Journal of the Reticuloendothelial Society最新文献

The development of transport ability by follicle-associated epithelium was studied in embryonic chick bursae. Developing lymphoid follicles were divided into three morphological types to determine the relationship of epithelial function to lymphoid development. Transport ability was first observed on day 13, two days earlier than obvious morphological evidence of follicle-associated epithelial development. Functional differentiation of the epithelium was, however, closely associated with lymphoid development rather than a day-specific developmental event. It is probable that the lymphoid cells have an inductive influence on the development of the overlying epithelium. Evidence of early embryonic transport by relatively undifferentiated epithelium also suggests that lymphoid development in the bursa may be influenced by epithelial transport.

The role of macrophages in the innate immunity of mice to histoplasmosis was investigated using silica, which selectively inactivates macrophages. Mice given silica IV 1 day prior to challenge with live yeast cells of Histoplasma capsulatum were more susceptible to infection than were untreated controls. This increased susceptibility to Histoplasma was observed when mice were given silica at 1, 14, and 21 days prior to infection but not at 3 and 7 days. Silica treated mice that survived 30 days after challenge with a sublethal dose of Histoplasma had 23 times more viable organisms in their spleens than in those of untreated controls. The blastogenic response of spleen cells to concanavalin A and phytohemagglutinin was unaffected at 12 hr after silica injection but was significantly depressed between 1 and 21 days. In contrast, silica treatment did not affect the blastogenic response of spleen cells to lipopolysaccharide. Silica particles were cytotoxic for mouse peritoneal macrophages but not to lymphocytes in vitro. These results indicate that macrophages play an essential role in natural immunity to histoplasmosis.

Purified supernatants obtained from human macrophage supernatants or the U937 human macrophage cell line are cytotoxic for tumor cells in vitro, and when tumor bearing animals are injected with these supernatants tumor growth is suppressed in vivo. Tumor growth rate and survival times were assessed for each group of animals. At day 12 after injection of the P815 tumor cells, no difference in tumor size could be demonstrated in any of the groups. However, by day 17 the tumors in the animals treated with macrophage supernatants or the U937 macrophage cell line supernatants did not continue to increase in size as was seen in the case of the control animals. When examining survival times, it appeared that the animals treated with macrophage supernatants survived approximately 8 days longer than did the animals receiving no treatment (35-day vs 27-day survival), and the animals treated with the U937 macrophage cell line supernatants survived approximately 13 days longer than the control animals (40-day vs 27-day survival). Thus, it appears that tumor cell growth can be slowed down in vivo when purified macrophage supernatants as well as the secretions from a human macrophage cell line are injected into the tumor mass.

Particulate yeast glucan, prepared by the methods of Northcote and Horne and Peat et al, was studied in rats and mice to determine its protective capacity in respiratory infection. Glucan was administered intravenously to rodents prior to infection with aerosols of bacteria. Glucan-treated rats had significantly increased rates of phagocytosis and killing of Staphylococcus aureus immediately after infection and minimal increases at 4 h. In contrast, pulmonary killing of Klebsiella pneumoniae in rats was markedly enhanced by glucan at 4 h. Glucan treatment of mice provided only transient protection against pulmonary infection with group C streptococci. Histological studies demonstrated greatly increased numbers of macrophages in the lungs of glucan-treated rats; the lungs of glucan-treated mice appeared normal. These results show that glucan can enhance intrapulmonary bacterial killing. In rats, this is due to the ability of glucan to increase the number of lung macrophages resulting in increased bacterial ingestion. Glucan-induced protection in mice is less clear.

A high-performance liquid chromatography (HPLC) purified fluorescein-labeled analogue of tuftsin was prepared, which retains the full biological activity of the native molecule. Characterization of the derivatization site by amino acid analysis, N-terminal cleavage, and dansylation revealed a monofluorescinated derivative at the alpha-amino terminus. Binding of the fluorescent tuftsin to living polymorphonuclear leukocytes (PMN) was observed by means of video intensification microscopy. At 37 degrees C, diffuse membrane fluorescence was seen initially, followed by rapid aggregation and internalization. The latter was demonstrated by saltation of intracellular fluorescent aggregates. These processes are temperature-dependent and rely on specific binding to the tuftsin receptor.

The fraction of macrophages and tumor cells in the DNA synthetic phase of the cell cycle was determined for the transplantable fibrosarcomas, RIF and KHT tumors, the mammary tumors EMT6, S102, and 67A, the B 16 melanoma, and the Lewis lung carcinoma. Thirty minutes after intraperitoneal injection of 3HTdR (tritiated thymidine), 10% to 28% of the macrophages were labeled. A similar proportion of tumor cells was labeled. This represents a high degree of local proliferation for macrophages in situ. Thus, macrophages can proliferate in growing tumors, and this local proliferation may represent an important source of these host defense cells.

The removal of carbon and turbot erythrocytes (TRBC) from the circulation of plaice, acclimated for 7 days at temperatures between 5 and 19 degrees C, revealed similar biphasic clearance patterns with up to 90% of particles removed over the first 30 min. There was no statistically significant difference in the rate of clearance over this wide temperature range. Organ localization of 51Cr-labeled TRBC at 12 degrees C revealed the kidney and spleen as the main phagocytic organs. Carbon-blockade experiments resulted in a significant depression of subsequent 51Cr-TRBC uptake by the kidney, although the spleen was unaffected. In the plaice there was no compensatory organ uptake, such as by the spleen in blockaded mammals, and particles persisted in the circulation.

Acquired resistance to listeriosis is thought to require immunological activation of mononuclear phagocytes to an enhanced microbicidal state. In this study we found that both neutrophils and mononuclear phagocytes from nonimmunized human donors killed Listeria monocytogenes in vitro as well as they killed Salmonella typhimurium and Escherichia coli. Bactericidal activity was detectable using both adherent cell and cell suspension bactericidal assays; however, bactericidal activity was greater when the suspension assay was used. Perhaps more surprising, freshly-obtained monocytes were more bactericidal than were monocytes cultured in vitro for 5-7 days, even though monocytes cultured in vitro acquire many characteristics of mature macrophages. These data suggest that newly emigrated monocytes and neutrophils may be particularly effective cell types in resistance to listeriosis.

Macrophage subpopulations having bactericidal or tumoricidal activities and secreting interleukin I (IL1) or prostaglandin E (PGE) were identified through primary or secondary infection with Salmonella enteritidis and separated by sedimentation velocity. Bactericidal activity was measured by [3H]-thymidine release from Listeria monocytogenes and tumoricidal activity by 51Cr-release from C-4 fibrosarcoma or P815 mastocytoma cells. Macrophages with bactericidal activity were distinguished from those with tumoricidal activity a) during secondary infection when cytolytic activity occurred only at days 1-4 post injection and bactericidal activity remained high throughout and b) after sedimentation velocity separation. Cytolysis was consistently greatest among adherent cells of low sedimentation velocity, whereas cells with bactericidal activity increased in size during the infection. Tumour cytostasis (inhibition and promotion of [3H]-thymidine uptake) differed from cytolysis in that the former was more prolonged during infection and was also detected among large cells. Secretion of immunoregulatory molecules PGE and IL1 occurred maximally among different macrophage subpopulations separated by sedimentation velocity and depending on the type of stimulus used in vitro. There was an inverse correlation between IL1 production and PGE production after stimulation with C3-zymosan or lipopolysaccharide (LPS). The development of immunity during infection may therefore be dependent upon the relative proportions of effector and regulatory macrophage subpopulations and the selective effects of environmental stimuli on these functions.

The possibility that the requirement for macrophages in the induction of an immune response is related to the antigen (Ag)-binding capacity of the lymphocyte populations that undergo activation has been examined. Spleen cells from mice immunized with 2,4,6-trinitrophenyl (TNP)-conjugated sheep red blood cells (TNP-SRBC) were filtered on a TNP-substituted Bio Gel column. The excluded cells were shown to be mainly low-affinity anti-TNP cells by using an anti-TNP plaque-forming assay and assessing the avidity of the plaque forming cells (PFC). In order to obtain a low-affinity anti-TNP precursor cell population, lymphocytes from nonimmunized mice were filtered as above. Unfiltered and filtered excluded nonimmune cells were cultured in the presence of Ag-pulsed macrophages or with the supernatants of the pulsed macrophage cultures. The filtered cells produced a specific antibody response only in the presence of the Ag-pulsed macrophages, while the total (nonfiltered) lymphocyte population contained PFC when cultured with free antigen. Determination of the avidity of the PFC confirmed the presence of low-affinity cells in the filtered population and the high affinity of the antibody-producing cells cultured in the absence of macrophages. The induction of a response in low-affinity lymphocytes appeared to require the presence of macrophages rather than that of a soluble factor present in the supernatant. It is suggested that the Ag-presenting role of macrophages are essential for the induction of the immune response in low-affinity cells, while high-affinity lymphocytes could be directly activated by free Ag.