Pub Date : 2021-01-01DOI: 10.15789/1563-0625-eob-2091
A. Dawood, Mahmood A. A. Altobje, Zeyad T. Alrassam
Background: Hepatitis B is the main infection of the injured liver for humans. Inflammation of the liver is caused by hepatitis viruses may lead to cirrhosis and hepatocellular carcinoma. The B-cell stimulatory factor 2 (BSF-2) is one of the cytokines that affect the regulation and differentiation of the human immune response. Objective: this report aims to estimate the BSF-2, GPT, and GOT levels in patients’ serum with different stages of hepatitis B compared with healthy control. Methods: This study assessed 52 patients presumably with acute and chronic cases who have HBsAg positive. BSF-2 was detected using ELISA assay. Biochemical parameters were determined using kits of an automated analyzer. SPSS version-16 software was used for statistical analysis. Results: Acute hepatitis B patients had shown elevation in BSF-2 level more than of chronic hepatitis B. GPT and GOT levels elevated in the acute hepatitis group more than of the chronic hepatitis group. We reported a significant value between BSF-2, GOT, and GPT levels. We didn’t score an association between patient’s age and cases groups of hepatitis. Conclusion: our data confirmed increasing of BSF-2 levels with the increase of GOT level more than GPT level with acute hepatitis B. BSF-2, GPT and GOT levels are varied in different courses of acute and chronic HBV. We surmised that the elevation of BSF-2 levels designates liver injury of patients with acute HBV.
{"title":"Elevation of BSF-2 Level in Serum of Patients with Hepatitis B Virus","authors":"A. Dawood, Mahmood A. A. Altobje, Zeyad T. Alrassam","doi":"10.15789/1563-0625-eob-2091","DOIUrl":"https://doi.org/10.15789/1563-0625-eob-2091","url":null,"abstract":"Background: Hepatitis B is the main infection of the injured liver for humans. Inflammation of the liver is caused by hepatitis viruses may lead to cirrhosis and hepatocellular carcinoma. The B-cell stimulatory factor 2 (BSF-2) is one of the cytokines that affect the regulation and differentiation of the human immune response. Objective: this report aims to estimate the BSF-2, GPT, and GOT levels in patients’ serum with different stages of hepatitis B compared with healthy control. Methods: This study assessed 52 patients presumably with acute and chronic cases who have HBsAg positive. BSF-2 was detected using ELISA assay. Biochemical parameters were determined using kits of an automated analyzer. SPSS version-16 software was used for statistical analysis. Results: Acute hepatitis B patients had shown elevation in BSF-2 level more than of chronic hepatitis B. GPT and GOT levels elevated in the acute hepatitis group more than of the chronic hepatitis group. We reported a significant value between BSF-2, GOT, and GPT levels. We didn’t score an association between patient’s age and cases groups of hepatitis. Conclusion: our data confirmed increasing of BSF-2 levels with the increase of GOT level more than GPT level with acute hepatitis B. BSF-2, GPT and GOT levels are varied in different courses of acute and chronic HBV. We surmised that the elevation of BSF-2 levels designates liver injury of patients with acute HBV.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67109281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01DOI: 10.15789/1563-0625-pti-2012
S. Bochkareva, I. Fedorova, O. Ershova, S. I. Koteleva, I. Kapustin, M. Blyakher, L. Novikova, A. Aleshkin, А. М. Vorobev
Our report concerns the observations made during the treatment of pneumonia with individually selected bacteriophages in HCAI patients on mechanical ventilation. 19 patients on mechanical ventilation whose condition was complicated by antibiotic-resistant pneumonia were examined. The treatment of patients was supplemented with phage therapy, bacteriophages were selected individually for each patient, taking into account the microbial etiology of the disease (Pseudomonas aeruginosa, Кlebsiella pneumoniae, Acinetobacter baumanii). Immunophenotyping of blood lymphocytes was carried out using 2-3-parameter flow cytometry. The functional activity of blood leukocytes was assessed by their ability to produce IFNα and IFNγ during cultivation. The level of interferons production in supernatants collected after cultivation was quantitatively evaluated both by their concentration (ELISA, reagents from “Vector-Best-Europe”, Russia) and by their biological activity. Statistical processing of the results was carried out using the Statistica 6 program according to the nonparametric Mann-Whitney U-test. In the course of successful phage therapy with individually selected bacteriophages overcoming of lymphopenia (if there was one) and an increase in both the number and functional activity of peripheral blood lymphocytes in all patients with pneumonia observed are noted. The relationship between the microbial load (mono- or mixed infection, the number of CFU pathogens of pneumonia, the need for repeated courses of phage therapy) and the degree of deficiency in one or another subpopulation of lymphocytes was not detected. Activation of the immune system achieved after one course of phage therapy was maintained for at least 3 weeks after phage administration was discontinued.
{"title":"Phage therapy in antibiotic resistant pneumonia: immunomodulation or redistribution?","authors":"S. Bochkareva, I. Fedorova, O. Ershova, S. I. Koteleva, I. Kapustin, M. Blyakher, L. Novikova, A. Aleshkin, А. М. Vorobev","doi":"10.15789/1563-0625-pti-2012","DOIUrl":"https://doi.org/10.15789/1563-0625-pti-2012","url":null,"abstract":"Our report concerns the observations made during the treatment of pneumonia with individually selected bacteriophages in HCAI patients on mechanical ventilation. 19 patients on mechanical ventilation whose condition was complicated by antibiotic-resistant pneumonia were examined. The treatment of patients was supplemented with phage therapy, bacteriophages were selected individually for each patient, taking into account the microbial etiology of the disease (Pseudomonas aeruginosa, Кlebsiella pneumoniae, Acinetobacter baumanii). Immunophenotyping of blood lymphocytes was carried out using 2-3-parameter flow cytometry. The functional activity of blood leukocytes was assessed by their ability to produce IFNα and IFNγ during cultivation. The level of interferons production in supernatants collected after cultivation was quantitatively evaluated both by their concentration (ELISA, reagents from “Vector-Best-Europe”, Russia) and by their biological activity. Statistical processing of the results was carried out using the Statistica 6 program according to the nonparametric Mann-Whitney U-test. In the course of successful phage therapy with individually selected bacteriophages overcoming of lymphopenia (if there was one) and an increase in both the number and functional activity of peripheral blood lymphocytes in all patients with pneumonia observed are noted. The relationship between the microbial load (mono- or mixed infection, the number of CFU pathogens of pneumonia, the need for repeated courses of phage therapy) and the degree of deficiency in one or another subpopulation of lymphocytes was not detected. Activation of the immune system achieved after one course of phage therapy was maintained for at least 3 weeks after phage administration was discontinued.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67111288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-12-01DOI: 10.15789/1563-0625-ivm-1975
E. Blinova, A. V. Kolerova, V. E. Balyasnikov, V. Kozlov
IL-7 is a key factor for the survival and maintenance of CD4+ central (Tcm) and effector (Tem) memory cells in the whole body. In many autoimmune diseases, an elevated level of IL-7 is detected in blood serum and at the site of inflammation, thus suggesting participation of this homeostatic factor in the survival of memory T cells, including auto-reactive clones, in inflammatory disorders. The aim of the study was to investigate the mechanisms of maintaining CD4+ memory T cells under normal and inflammatory conditions. We developed an in vitro model of inflammation, based on induction of pro-inflammatory cytokines, and then evaluated the effects of IL-7 upon purified sorted populations of CD4+Tcm and Tem under normal conditions and in vitro inflammatory model. IL-7 treatment promoted maintenance of CD4+Tcm phenotype in all variants of cultures. In the absence of contact with adherent cell fraction, the IL-7-induced proliferation of Tcm and Tem was slightly reduced, both under normal and inflammatory conditions, thus suggesting low sensitivity of memory T cells to contacts with MHC, and, probably, a requirement for additional signals to provide complete stimulation with IL-7. The last suggestion is also supported by data about CD127 and CD132 expression, i.e., in the absence of contact with MHC, the proportion of CD127+CD132+ cells was decreased in both subpopulations of CD4+ memory cells. Upon in vitro cultures, IL-7 contributed to decreased expression of CD127, and increased expression of CD132 on CD4+Tcm and Tem. We have evaluated the CD4+Tcm and Tem populations by affinity of T cell receptor (TCR), using the level of CD5 expression. Т cells with high TCR affinity for self-antigens are known to have higher expression of CD5. In comparison to Tem, the Tcm contained more CD5high cells. In cultures, IL-7 promoted a high level of CD5 expression on Tcm, which was comparable to levels observed in peripheral blood cells. High CD5 expression on Tem was observed after stimulation with IL-7 in the in vitro inflammatory model. In the absence of contact with MHC, the number of CD5high cells decreased among CD4+Tem and Tcm. Thus, CD4+Tcm cells with high affinity for autologous antigens are probably dependent on the presence of homeostatic factors, in particular, IL-7, and contacts with antigen-presenting cells (APCs). Under conditions of inflammation, no changes were revealed in the mechanism of maintaining CD4+Tcm, in contrast to CD4+Tem. Being less dependent on IL-7 under normal conditions, CD4+CD5highTem are accumulated in the presence of IL-7 under in vitro inflammatory conditions.
{"title":"In vitro maintaining of CD4+ central and effector memory cells in normal and inflammatory conditions","authors":"E. Blinova, A. V. Kolerova, V. E. Balyasnikov, V. Kozlov","doi":"10.15789/1563-0625-ivm-1975","DOIUrl":"https://doi.org/10.15789/1563-0625-ivm-1975","url":null,"abstract":"IL-7 is a key factor for the survival and maintenance of CD4+ central (Tcm) and effector (Tem) memory cells in the whole body. In many autoimmune diseases, an elevated level of IL-7 is detected in blood serum and at the site of inflammation, thus suggesting participation of this homeostatic factor in the survival of memory T cells, including auto-reactive clones, in inflammatory disorders. The aim of the study was to investigate the mechanisms of maintaining CD4+ memory T cells under normal and inflammatory conditions. We developed an in vitro model of inflammation, based on induction of pro-inflammatory cytokines, and then evaluated the effects of IL-7 upon purified sorted populations of CD4+Tcm and Tem under normal conditions and in vitro inflammatory model. IL-7 treatment promoted maintenance of CD4+Tcm phenotype in all variants of cultures. In the absence of contact with adherent cell fraction, the IL-7-induced proliferation of Tcm and Tem was slightly reduced, both under normal and inflammatory conditions, thus suggesting low sensitivity of memory T cells to contacts with MHC, and, probably, a requirement for additional signals to provide complete stimulation with IL-7. The last suggestion is also supported by data about CD127 and CD132 expression, i.e., in the absence of contact with MHC, the proportion of CD127+CD132+ cells was decreased in both subpopulations of CD4+ memory cells. Upon in vitro cultures, IL-7 contributed to decreased expression of CD127, and increased expression of CD132 on CD4+Tcm and Tem. We have evaluated the CD4+Tcm and Tem populations by affinity of T cell receptor (TCR), using the level of CD5 expression. Т cells with high TCR affinity for self-antigens are known to have higher expression of CD5. In comparison to Tem, the Tcm contained more CD5high cells. In cultures, IL-7 promoted a high level of CD5 expression on Tcm, which was comparable to levels observed in peripheral blood cells. High CD5 expression on Tem was observed after stimulation with IL-7 in the in vitro inflammatory model. In the absence of contact with MHC, the number of CD5high cells decreased among CD4+Tem and Tcm. Thus, CD4+Tcm cells with high affinity for autologous antigens are probably dependent on the presence of homeostatic factors, in particular, IL-7, and contacts with antigen-presenting cells (APCs). Under conditions of inflammation, no changes were revealed in the mechanism of maintaining CD4+Tcm, in contrast to CD4+Tem. Being less dependent on IL-7 under normal conditions, CD4+CD5highTem are accumulated in the presence of IL-7 under in vitro inflammatory conditions.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"22 1","pages":"837-846"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45735461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-12-01DOI: 10.15789/1563-0625-ios-2006
V. G. Zolotykh, A. Gvozdetsky, A. Y. Kim, S. Lapin, L. Mikhailova, E. M. Starovoitova, T. Fedotkina, L. Churilov, Y. Schoenfeld, P. Yablonsky
The article concerns a study of early influence of silicone breast implants on the development of autoimmune reactions and dynamics of prolactin and thyroid hormone levels in women after mammoplasty. At the present time, this issue remains relevant for several reasons: more than 20 million pairs of implants have been installed in the world and the number of their implantations is constantly growing. Despite relative safety of the silicone implants, some of them are periodically banned by regulatory bodies in various countries. At the same time, there is a growing number of controversial publications in the scientific literature, about potential adverse consequences of their use. Some authors suggest an association between the silicone implants and risk of developing autoimmune conditions, connective tissue disorders, and occasional malignancies. On the other hand, the journals are full of publications about the overall safe tolerance of such medical devices by the patients. These considerations served as a pre-requisite to our research. As part of this project, we have assayed serum levels of autoantibodies to ten antigens, as well as contents of prolactin and thyroid hormones by means of ELISA technique in 27 patients before, 3 and 6 months after aesthetic and reconstructive mammoplastics performed within a period of September 2018 to November 2019. As a result, it was found that 5 out of 27 patients exhibited changes in the autoimmunity spectrum and intensity after mammoplasty. In particular, the concentrations of autoantibodies to modified citrullinated vimentin and IgM autoantibodies to cardiolipin exceeded the normal level at 3 and 6 months. In addition, the initially high prolactin concentration in mammoplasty recipients dropped to normal ranges by 3 months after breast surgery, even after several-fold increased initial levels. As for thyroid hormones, there were no statistically significant changes in their dynamics. The increase of autoantibodies to various target antigens after mammoplasty was statistically significant and positively correlated with each other. This can be explained, for example, by dependence on the adjuvant effect of silicone, which is not associated with antigen specificity. However, it may generally stimulate the immune responses.
{"title":"Influence of silicone mammoplasty on the immunoendocrine status of female recipients","authors":"V. G. Zolotykh, A. Gvozdetsky, A. Y. Kim, S. Lapin, L. Mikhailova, E. M. Starovoitova, T. Fedotkina, L. Churilov, Y. Schoenfeld, P. Yablonsky","doi":"10.15789/1563-0625-ios-2006","DOIUrl":"https://doi.org/10.15789/1563-0625-ios-2006","url":null,"abstract":"The article concerns a study of early influence of silicone breast implants on the development of autoimmune reactions and dynamics of prolactin and thyroid hormone levels in women after mammoplasty. At the present time, this issue remains relevant for several reasons: more than 20 million pairs of implants have been installed in the world and the number of their implantations is constantly growing. Despite relative safety of the silicone implants, some of them are periodically banned by regulatory bodies in various countries. At the same time, there is a growing number of controversial publications in the scientific literature, about potential adverse consequences of their use. Some authors suggest an association between the silicone implants and risk of developing autoimmune conditions, connective tissue disorders, and occasional malignancies. On the other hand, the journals are full of publications about the overall safe tolerance of such medical devices by the patients. These considerations served as a pre-requisite to our research. As part of this project, we have assayed serum levels of autoantibodies to ten antigens, as well as contents of prolactin and thyroid hormones by means of ELISA technique in 27 patients before, 3 and 6 months after aesthetic and reconstructive mammoplastics performed within a period of September 2018 to November 2019. As a result, it was found that 5 out of 27 patients exhibited changes in the autoimmunity spectrum and intensity after mammoplasty. In particular, the concentrations of autoantibodies to modified citrullinated vimentin and IgM autoantibodies to cardiolipin exceeded the normal level at 3 and 6 months. In addition, the initially high prolactin concentration in mammoplasty recipients dropped to normal ranges by 3 months after breast surgery, even after several-fold increased initial levels. As for thyroid hormones, there were no statistically significant changes in their dynamics. The increase of autoantibodies to various target antigens after mammoplasty was statistically significant and positively correlated with each other. This can be explained, for example, by dependence on the adjuvant effect of silicone, which is not associated with antigen specificity. However, it may generally stimulate the immune responses.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"22 1","pages":"957-968"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46279847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-12-01DOI: 10.15789/1563-0625-rbu-2001
R. Sholan
The purpose of this work was to study the relationships between urinary cytokines, mast cells and nerve growth factor (NGF) in the patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Sixty-eight women with clinically diagnosed IC/BPS were under study. Their mean age was 54.2±12.4 years. Urinary concentrations of interleukins (IL-1β, IL-6, IL-8), tumor necrosis factor-α (TNFα), and NGF were determined by ELISA technique. Mast cells were identified in biopsies of mucous membranes from urinary bladder harvested during cystoscopy. Statistical evaluation was performed by Statistica program in Microsoft Excel. Pearson correlation quotients were calculated. Depending on the type of IC/BPS, the patients were divided into 2 groups: group I included 36 patients with classic type of disease; group II comprised 32 patients with non-ulcer type of IC/BPS. No significant differences were revealed between the groups. In 13.9% of patients from group I, the onset of clinical manifestations of the disease was observed at the age of less than 40 years; in group II, 28.1% of the examined mentioned appearance of the disease symptoms at this age. The levels of IL-1β in the patients from group I was 2.4 times higher than in controls (p < 0.05). IL-6, IL-8 and TNFα concentrations exceeded control values by 2.0 (p < 0.05), 2.5 (p < 0.05) and 2.0 times (p < 0.05), respectively. In the patients from group II, the content of IL-1β, IL-6, IL-8 and TNFα was 2.4 (p < 0.05), 2.0 (p < 0.05), 2.0 (p < 0.05) and 1.9 (p < 0.05) times higher than in the control group, respectively. There were no significant differences between groups I and II, in IL-1β, IL-6, and TNFα levels, except of IL-8 in women of group I that was 20.3% higher than in group II. The urinary NGF level in the patients with IC/BPS exceeded the control level 1.6 times (p < 0.05) for group I, and 1.5 times (p < 0.05) for group II. The number of mast cells in the patients of group I was significantly higher than in controls and in group II, i.e., 1.6 (p < 0.05) and 1.4 times (p < 0.05), respectively. In most cases, a direct weak correlation was revealed between the indices. Only in group I, a moderate correlation (r = + 0.508) could be detected between IL-1β and mast cells. Determination of cytokine levels allows to detect activation of inflammatory cells in bladder tissue and provides an opportunity for developing diagnostic strategies. Increased numbers of mast cells may indicate the importance of these cells in the disease progression, whereas elevated levels of NGF in urine suggests that IC/BPS may be caused by chronic inflammation.
{"title":"Relationships between urinary neural and immune factors in the patients with interstitial cystitis/ bladder painful syndrome","authors":"R. Sholan","doi":"10.15789/1563-0625-rbu-2001","DOIUrl":"https://doi.org/10.15789/1563-0625-rbu-2001","url":null,"abstract":"The purpose of this work was to study the relationships between urinary cytokines, mast cells and nerve growth factor (NGF) in the patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Sixty-eight women with clinically diagnosed IC/BPS were under study. Their mean age was 54.2±12.4 years. Urinary concentrations of interleukins (IL-1β, IL-6, IL-8), tumor necrosis factor-α (TNFα), and NGF were determined by ELISA technique. Mast cells were identified in biopsies of mucous membranes from urinary bladder harvested during cystoscopy. Statistical evaluation was performed by Statistica program in Microsoft Excel. Pearson correlation quotients were calculated. Depending on the type of IC/BPS, the patients were divided into 2 groups: group I included 36 patients with classic type of disease; group II comprised 32 patients with non-ulcer type of IC/BPS. No significant differences were revealed between the groups. In 13.9% of patients from group I, the onset of clinical manifestations of the disease was observed at the age of less than 40 years; in group II, 28.1% of the examined mentioned appearance of the disease symptoms at this age. The levels of IL-1β in the patients from group I was 2.4 times higher than in controls (p < 0.05). IL-6, IL-8 and TNFα concentrations exceeded control values by 2.0 (p < 0.05), 2.5 (p < 0.05) and 2.0 times (p < 0.05), respectively. In the patients from group II, the content of IL-1β, IL-6, IL-8 and TNFα was 2.4 (p < 0.05), 2.0 (p < 0.05), 2.0 (p < 0.05) and 1.9 (p < 0.05) times higher than in the control group, respectively. There were no significant differences between groups I and II, in IL-1β, IL-6, and TNFα levels, except of IL-8 in women of group I that was 20.3% higher than in group II. The urinary NGF level in the patients with IC/BPS exceeded the control level 1.6 times (p < 0.05) for group I, and 1.5 times (p < 0.05) for group II. The number of mast cells in the patients of group I was significantly higher than in controls and in group II, i.e., 1.6 (p < 0.05) and 1.4 times (p < 0.05), respectively. In most cases, a direct weak correlation was revealed between the indices. Only in group I, a moderate correlation (r = + 0.508) could be detected between IL-1β and mast cells. Determination of cytokine levels allows to detect activation of inflammatory cells in bladder tissue and provides an opportunity for developing diagnostic strategies. Increased numbers of mast cells may indicate the importance of these cells in the disease progression, whereas elevated levels of NGF in urine suggests that IC/BPS may be caused by chronic inflammation.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"22 1","pages":"879-886"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46862169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-12-01DOI: 10.15789/1563-0625-sot-2051
M. Bochkova, V. Timganova, P. Khramtsov, S. Uzhviyuk, K. Shardina, A. Nechaev, M. Raev, S. Zamorina
Graphene and its derivatives are increasingly used in biomedical research. Therefore, the mechanisms and consequences of the interaction of graphene nanoparticles with living objects are intensively studied. The immune system is involved in protecting the body and regulating its functions, so the question of the effect of graphene and its derivatives on immune cells is crucial. The specific response of monocytes, macrophages, and neutrophils to a stimulus is to increase the production of reactive oxygen species (ROS). Published data on graphene oxide (GO) and polyethylene glycol-modified graphene oxide (GO-PEG) effects on peripheral blood leukocytes are scarce and contradictory. It is due to variations in objects and conditions of study, along with the difference in particle concentrations. Thus, it was essential to evaluate the GO and GO-PEG effect on ROS production by human leukocytes. Our study aimed at the effect of particles of unmodified and PEG-modified graphene oxide (GO and GO-PEG) on the ROS production by peripheral blood leukocytes in not-stimulated and stimulated luminoldependent chemiluminescence (LCL) tests. ROS production was stimulated by opsonized zymosan (OZ). A hydrogen peroxide-luminol system was used for assessing the independent effect of GO nanoparticles on the quenching of ROS luminescence. Pristine GO (Ossila, Great Britain) nanoparticles were PEG-modified (GO-PEG). The average size of the GO flakes was 1-5 µm, the GO-PEG-flakes 569±14 nm, and the amount of PEG covering was ~ 20%. Nanoparticles were used at concentrations of 5; 2.5; 1.25 µg/ml. It has been established that GO-PEG nanoparticles in concentrations of 2.5 and 5 µg/ml suppressed ROS production in the spontaneous LCL test. At the same time, the GO effects showed a visible but a not significant tendency to inhibition of LCL. Similar results were obtained in the stimulated LCL test. However, when analyzing the process kinetics, both GO-PEG and GO decreased the ROS production, but mainly in the first minutes of the test. When analyzing the quenching effect of the LCL reaction in a cell-free system, there was no significant effect of GO and GO-PEG nanoparticles. Thus, the general vector of the obtained effects was associated with the suppression of ROS production. GO-PEG ROS-decreasing effects were more pronounced in comparison with unmodified GO. In general, we have confirmed the antioxidant effects of GO and GO-PEG using the LCL method. We can assume that in addition to the actual antioxidant effect of graphene nanoparticles, ROS production decreases due to the rapid GO uptake and blocking of several intracellular signals that induce an oxidative burst.
{"title":"Study of the graphene oxide nanoparticles effect on luminol-dependent chemiluminescence of human leukocytes","authors":"M. Bochkova, V. Timganova, P. Khramtsov, S. Uzhviyuk, K. Shardina, A. Nechaev, M. Raev, S. Zamorina","doi":"10.15789/1563-0625-sot-2051","DOIUrl":"https://doi.org/10.15789/1563-0625-sot-2051","url":null,"abstract":"Graphene and its derivatives are increasingly used in biomedical research. Therefore, the mechanisms and consequences of the interaction of graphene nanoparticles with living objects are intensively studied. The immune system is involved in protecting the body and regulating its functions, so the question of the effect of graphene and its derivatives on immune cells is crucial. The specific response of monocytes, macrophages, and neutrophils to a stimulus is to increase the production of reactive oxygen species (ROS). Published data on graphene oxide (GO) and polyethylene glycol-modified graphene oxide (GO-PEG) effects on peripheral blood leukocytes are scarce and contradictory. It is due to variations in objects and conditions of study, along with the difference in particle concentrations. Thus, it was essential to evaluate the GO and GO-PEG effect on ROS production by human leukocytes. Our study aimed at the effect of particles of unmodified and PEG-modified graphene oxide (GO and GO-PEG) on the ROS production by peripheral blood leukocytes in not-stimulated and stimulated luminoldependent chemiluminescence (LCL) tests. ROS production was stimulated by opsonized zymosan (OZ). A hydrogen peroxide-luminol system was used for assessing the independent effect of GO nanoparticles on the quenching of ROS luminescence. Pristine GO (Ossila, Great Britain) nanoparticles were PEG-modified (GO-PEG). The average size of the GO flakes was 1-5 µm, the GO-PEG-flakes 569±14 nm, and the amount of PEG covering was ~ 20%. Nanoparticles were used at concentrations of 5; 2.5; 1.25 µg/ml. It has been established that GO-PEG nanoparticles in concentrations of 2.5 and 5 µg/ml suppressed ROS production in the spontaneous LCL test. At the same time, the GO effects showed a visible but a not significant tendency to inhibition of LCL. Similar results were obtained in the stimulated LCL test. However, when analyzing the process kinetics, both GO-PEG and GO decreased the ROS production, but mainly in the first minutes of the test. When analyzing the quenching effect of the LCL reaction in a cell-free system, there was no significant effect of GO and GO-PEG nanoparticles. Thus, the general vector of the obtained effects was associated with the suppression of ROS production. GO-PEG ROS-decreasing effects were more pronounced in comparison with unmodified GO. In general, we have confirmed the antioxidant effects of GO and GO-PEG using the LCL method. We can assume that in addition to the actual antioxidant effect of graphene nanoparticles, ROS production decreases due to the rapid GO uptake and blocking of several intracellular signals that induce an oxidative burst.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"22 1","pages":"977-986"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45196024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-12-01DOI: 10.15789/1563-0625-son-1991
T. Y. Abramova, E. Blinova, L. Grishina, O. Chumasova, A. E. Sulut’yan, A. Sizikov, V. Kozlov
The process of apoptosis is known that play an important role in cellular homeostasis, and the altered cell death may lead to development of pathological disorders. Evolving autoimmune conditions, in particular, rheumatoid arthritis, are associated with decreased rates of apoptosis as a form of programmed cell death. The aim of this study was to evaluate expression of activation and proliferation markers on T lymphocytes during initiation of apoptotic cell death under the conditions of “cell neighborhood” in healthy individuals and patients with rheumatoid arthritis. Patients and methods. The study was performed with blood samples of the patients with rheumatoid arthritis (RA) and healthy women of comparable age. During the study, we conducted experiments aimed to identify the in vitro influence of non-stimulated apoptosis-induced cells, as well as aCD3- and dexamethasone (Dexa)-stimulated apoptosis-induced cells upon autologous T lymphocytes cultured under physiological conditions. Development of a “cell neighborhood” model, i.e., co-cultures of CFSE- T cells subjected to incubation under crowding condition and depletion of the culture medium which is the most physiological variant of apoptosis activation, and CFSE+ autologous cells placed in the complete culture medium, has revealed some relationships. We have revealed an opportunity of secondary induction of early and late apoptosis by means of humoral and cellular components of autologous cell culture subjected to activation apoptosis. We determined the features of apoptosis in unstimulated, as well as aCD3- and dexamethasone-stimulated cultures, compared with controls. There were no differences in these parameters of apoptosis between RA patients and healthy people for all variants of cultures. An increased proportion of viale cells was found in the CFSE- culture of patients with RA when compared to donors. The donor group had more lymphocytes with activation parameters CD25+, CD69+ and low level of proliferation marker Ki-67 than patients. In contrast to healthy, the RA patients demonstrated a significantly increased expression of Ki 67 in T lymphocytes when co-culturing CFSE- and CFSE+ cells. An increased number of living cells in apoptotic cultures of patients with RA relative to healthy people, in absence of significant differences in the parameters of apoptosis and activation markers in dynamics, as well as pattern of changes in the Ki-67+ cell contents suggested a contribution of the non-autonomous effects of apoptosis to cellular homeostasis in RA patients.
{"title":"Studies of non-autonomous effects of apoptosis in the course of in vitro apoptotic cell death initiation in healthy persons and patients with rheumatoid arthritis","authors":"T. Y. Abramova, E. Blinova, L. Grishina, O. Chumasova, A. E. Sulut’yan, A. Sizikov, V. Kozlov","doi":"10.15789/1563-0625-son-1991","DOIUrl":"https://doi.org/10.15789/1563-0625-son-1991","url":null,"abstract":"The process of apoptosis is known that play an important role in cellular homeostasis, and the altered cell death may lead to development of pathological disorders. Evolving autoimmune conditions, in particular, rheumatoid arthritis, are associated with decreased rates of apoptosis as a form of programmed cell death. The aim of this study was to evaluate expression of activation and proliferation markers on T lymphocytes during initiation of apoptotic cell death under the conditions of “cell neighborhood” in healthy individuals and patients with rheumatoid arthritis. Patients and methods. The study was performed with blood samples of the patients with rheumatoid arthritis (RA) and healthy women of comparable age. During the study, we conducted experiments aimed to identify the in vitro influence of non-stimulated apoptosis-induced cells, as well as aCD3- and dexamethasone (Dexa)-stimulated apoptosis-induced cells upon autologous T lymphocytes cultured under physiological conditions. Development of a “cell neighborhood” model, i.e., co-cultures of CFSE- T cells subjected to incubation under crowding condition and depletion of the culture medium which is the most physiological variant of apoptosis activation, and CFSE+ autologous cells placed in the complete culture medium, has revealed some relationships. We have revealed an opportunity of secondary induction of early and late apoptosis by means of humoral and cellular components of autologous cell culture subjected to activation apoptosis. We determined the features of apoptosis in unstimulated, as well as aCD3- and dexamethasone-stimulated cultures, compared with controls. There were no differences in these parameters of apoptosis between RA patients and healthy people for all variants of cultures. An increased proportion of viale cells was found in the CFSE- culture of patients with RA when compared to donors. The donor group had more lymphocytes with activation parameters CD25+, CD69+ and low level of proliferation marker Ki-67 than patients. In contrast to healthy, the RA patients demonstrated a significantly increased expression of Ki 67 in T lymphocytes when co-culturing CFSE- and CFSE+ cells. An increased number of living cells in apoptotic cultures of patients with RA relative to healthy people, in absence of significant differences in the parameters of apoptosis and activation markers in dynamics, as well as pattern of changes in the Ki-67+ cell contents suggested a contribution of the non-autonomous effects of apoptosis to cellular homeostasis in RA patients.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"22 1","pages":"847-866"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46170739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-12-01DOI: 10.15789/1563-0625-rbi-2059
E. I. Polozova, E. Puzanova, A. Seskina
Our study was aimed at assessing a relationship between immune system alterations, hypoxia and inflammation in arterial hypertension (AH) coupled to metabolic disturbances. A total of 117 patients were enrolled into clinical study, having been randomized into groups in accordance with study protocol, aged 30 to 62 years. They sought care in outpatient setting or underwent periodic health examination at the Republican Clinical Hospital №5, Saransk, Mordovia, Russia. A control group contained 25 apparently healthy subjects lacking signs of metabolic syndrome (MS) and elevated arterial pressure. A comparison group contained 47 patients with AH grade I-II featured with damaged target organs, but lacking associated relevant clinical manifestations, as based on the assay data. The main group contained 45 patients receiving antihypertensive therapy with overt AH grade I-II verified upon medical consultation coupled to damaged target organs and MS signs with its randomly combined components, but lacking associated clinical manifestations. The patients from main and comparison groups received antihypertensive therapy in accordance with approved guidelines and clinical recommendations for management of AH patients consisting of one of renin-angiotensin-aldosterone system blockers, diuretic and/or dihydropyridine calcium channel blocker. Cytokine profile, level of hypoxia and non-specific inflammation were measured in blood serum. The data obtained demonstrated that AH patients with/without metabolic syndrome were noted to display cytokine profile shifted towards elevated proand anti-inflammatory immune arm pointing at imbalanced immune regulation. Hypoxic changes were also found in blood serum that was confirmed by elevated level of lactic and pyruvic acid in these groups. Moreover, development of such pathology was coupled to hypoxia which served as a modulator of immune-related and non-specific inflammation. Rise of non-specific low-grade inflammation correlates developing irreversible AH-associated changes in organs, progression of atherosclerosis and accelerated cardio-metabolic continuum. Altogether, such alterations underlie pathogenetic mechanisms of tissue damage emerging upon AH and MS being mutually aggravating factor along with activated renin-angiotensin-aldosterone system.
{"title":"Relationship between immunological alterations, hypoxia and inflammation in arterial hypertension combined with metabolic syndrome","authors":"E. I. Polozova, E. Puzanova, A. Seskina","doi":"10.15789/1563-0625-rbi-2059","DOIUrl":"https://doi.org/10.15789/1563-0625-rbi-2059","url":null,"abstract":"Our study was aimed at assessing a relationship between immune system alterations, hypoxia and inflammation in arterial hypertension (AH) coupled to metabolic disturbances. A total of 117 patients were enrolled into clinical study, having been randomized into groups in accordance with study protocol, aged 30 to 62 years. They sought care in outpatient setting or underwent periodic health examination at the Republican Clinical Hospital №5, Saransk, Mordovia, Russia. A control group contained 25 apparently healthy subjects lacking signs of metabolic syndrome (MS) and elevated arterial pressure. A comparison group contained 47 patients with AH grade I-II featured with damaged target organs, but lacking associated relevant clinical manifestations, as based on the assay data. The main group contained 45 patients receiving antihypertensive therapy with overt AH grade I-II verified upon medical consultation coupled to damaged target organs and MS signs with its randomly combined components, but lacking associated clinical manifestations. The patients from main and comparison groups received antihypertensive therapy in accordance with approved guidelines and clinical recommendations for management of AH patients consisting of one of renin-angiotensin-aldosterone system blockers, diuretic and/or dihydropyridine calcium channel blocker. Cytokine profile, level of hypoxia and non-specific inflammation were measured in blood serum. The data obtained demonstrated that AH patients with/without metabolic syndrome were noted to display cytokine profile shifted towards elevated proand anti-inflammatory immune arm pointing at imbalanced immune regulation. Hypoxic changes were also found in blood serum that was confirmed by elevated level of lactic and pyruvic acid in these groups. Moreover, development of such pathology was coupled to hypoxia which served as a modulator of immune-related and non-specific inflammation. Rise of non-specific low-grade inflammation correlates developing irreversible AH-associated changes in organs, progression of atherosclerosis and accelerated cardio-metabolic continuum. Altogether, such alterations underlie pathogenetic mechanisms of tissue damage emerging upon AH and MS being mutually aggravating factor along with activated renin-angiotensin-aldosterone system.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"22 1","pages":"1003-1008"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47252728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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