International archives of allergy and applied immunology最新文献

Mast cells are involved in allergic reactions where they release numerous vasoactive and other mediators in response to IgE and antigen. They are also activated by neuropeptides and are found in close contact with neurons. Mast cell heterogeneity has now been documented for mucosal mast cells and connective tissue mast cells. Rat brain mast cells were studied in a perfusion system and were shown to release serotonin in response to the mast cell secretagogue compound 48/80 (C48/80). High-potassium neuronal depolarization also released serotonin, but this was calcium dependent, not associated with beta-hexosaminidase, and was unaffected by prior treatment with C48/80. Neuronal depolarization, however, was associated with somatostatin secretion and substantially reduced subsequent C48/80 stimulation, an effect abolished by neonatal treatment of the animals with capsaicin. Perfusion with somatostatin and substance P also induced brain mast cell serotonin release. C48/80 stimulation of combined thalamic and hypothalamic slices after neuronal depolarization substantially reduced the C48/80 effect, suggesting the possible presence of endogenous inhibitors released from the hypothalamus. Finally, the alpha 2-receptor agonist clonidine had a slight stimulatory effect. These results indicate that brain mast cell serotonin release may be regulated by endogenous neurotransmitters and/or neuromodulators.

A study was carried out on 29 patients to investigate the amount of histamine liberation and release of platelet-activating factor and 6-keto-prostaglandin F1 alpha from gastric mucosa and whole blood or mononuclear cells by sodium benzoate. The patients suffered from asthma (10), atopic dermatitis (7) and chronic urticaria (4). 8 patients with unrelated, non-immunologic diseases served as controls. In the oral provocation test (OPT) 3 patients experienced a recurrence of their original disease, whilst 1 asthmatic patient reacted with abdominal disorder. The release of histamine and prostaglandin from mucosa was significantly increased by sodium benzoate in comparison to the spontaneous release observed in patients. The mucosa of the control persons did not react to sodium benzoate. Furthermore, there was a significant difference in prostaglandin release between patients with positive OPT and the control persons. No difference could be found between patients with negative OPT and those with positive OPT. Additionally, in the mediator release from whole blood or mononuclear cells there was no obvious difference apparent. These results suggest a possible involvement of prostacyclin and histamine in adverse reactions to benzoate. Due to the sensitivity of the method, a mediator release from mucosa can already be demonstrated in a preclinical state of the pseudoallergic reaction in the absence of clinical symptoms.

We have applied immunoassays for complement activation products C4d, fragment Bb and the protein S-C5b-9 neoantigen (S-MAC) to assess activation of classical, alternative and terminal pathways, respectively, by lipopolysaccharides (LPS) from the smooth strain (SS) of Salmonella minnesota and the shallow rough (core) mutants R60, R345, R5 and R7. Incubations of sera (n = 6) with LPS generated small and insignificant quantities of Bb and S-MAC in the case of Rb, Rc and Rd chemotypes and slightly greater quantities with Ra. SS-LPS brought about significant (p = 0.01) increases in the formation of both Bb and S-MAC. No significant changes were observed in the concentration of C4d. Polymyxin B enhanced Bb and S-MAC production by SS-LPS, optimally at the lowest concentration of polymyxin B studied, 10 ng/ml. These data confirm and extend observations about complement activation by LPS and suggest that immunoassay may be useful in studying mechanisms of complement activation.

We investigated the capacity of excretory and secretory antigen (ES) derived from living filarial worms in the induction of CD23 expression on human peripheral blood T cells by using flow cytometry. ES (10 micrograms/ml) significantly induced the expression of CD23 on human T cells. Moreover, increased CD23 expression was completely abolished by preincubation with specific antibody to ES. The results suggest that ES might play a certain role in IgE antibody production by induction of CD23 expression on T cells.

Abnormalities of peripheral-blood lymphocyte subsets and activation markers were detected in patients with both allergic and nonallergic asthma. Most allergic asthmatics were characterized by increased numbers of IL-2R+ helper T cells and CD23+ B cells. In contrast, nonallergic asthmatics showed increased numbers of IL-2R+ and HLA-DR+ helper and cytotoxic T cells, and a clear redistribution from naive (CD45RA+) to memory (CD45RO+) cells. The number of IL-2R+ T cells correlated with the number of CD23+ B cells in allergic asthma. These changes in the distribution and activation state of T cells suggest an active role for T cells in the pathogenesis of both allergic and nonallergic asthma.

Subcutaneous treatment of guinea pigs with platelet-activating factor (PAF) caused an increase in the prevalence of eosinophils in lavage fluid recovered from pulmonary airways, and pleural and peritoneal cavities. In PAF-treated animals, total numbers of eosinophils and macrophages in washings were positively correlated, thus there was no apparent competition between the two cell types for migration at traffic sites into body cavities. The results indicate that PAF acts centrally to enhance the migration of eosinophils and monocytes into body cavities, perhaps by inducing bone marrow release of both classes of leucocytes which may then migrate constitutively into lung, pleural and peritoneal cavities.

Availability of reproducible mouse models for allergic contact dermatitis (ACD) to the metal allergens nickel, mercury and chromium, would be of great value for pathogenetic and preventive studies. We explored epicutaneous sensitization to nickel, mercury and chromium in mice in which oral grooming of the sensitization site was prevented by a plaster cast around the abdomen and lower thorax. This procedure was based on earlier findings that oral ingestion of allergen could prevent contact sensitization. The present results show that BALB/c mice can be readily sensitized to mercury and chromium using this epicutaneous casting method, without the further use of adjuvants. With nickel, however, neither this method, nor conventional methods involving the use of Freund's complete adjuvant (FCA) were effective.

Human polymorphonuclear leukocytes kill WEHI 164 cells in an 18-hour 51Cr release assay. Antibody to human tumor necrosis factor (TNF) blocks the lysis of targets mediated by human granulocytes. Resting granulocytes produce an undetectable amount of TNF, if any. Granulocytes stimulated with Staphylococcus aureus release 250-500 U/ml TNF alpha. The specificity of the released TNF in the WEHI 164 cytotoxicity assay was confirmed by using neutralizing anti-TNF alpha monoclonal antibodies. The thymidine uptake of endothelial cells was inhibited by granulocyte-derived TNF. The identity of TNF alpha was further confirmed by molecular weight determination, by gel filtration on Sephacryl S-200, with a result of approximately 44,000. Besides their antimicrobial capacity, therefore, granulocytes may contribute to tumor rejection, inflammation and septic infections by releasing TNF.