The overall objective of this project is to extend previous skin chamber and histologic studies in this lab to farther delineate underlying mechanisms in human allergic skin reactions. Specific objectives are to: 1) compare patterns of local mediator release induced by continuous vs interrupted antigen challenge and relate patterns and degrees of such responses to late phase cutaneous allergic reactions (LACR); 2) determine the cellular source of the continued low-level histamine release and the mechanisms underlying an antigen-specific desensitization developing during continuous antigen challenge; 3) determine the cell source of LTB4 and PAF secreted in such reactions; 4) determine whether neutrophil and eosinophil products released in such reaction sites have pathogenic effects on dermal components like elastin, collagen, vascular endothelium; 5) determine the intracellular pathways of neutrophil activation induced by factors released in allergic reaction sites: 6) determine whether factors released on allergic reaction sites; a) affect further mediator release in vivo and in vitro; b) affect function of lymphocytes and monocytes; 7) determine in biopsy studies: a) whether neutrophils become activated as they enter the dermis during allergic reactions; b) whether basophils could be a source of the local continued histamine release observed. These objectives will be approached by applying immunoassays, bioassays, enzyme assays, chromatography, and immunohistochemical techniques to studies of skin chamber and biopsy specimens. The hypotheses to be tested are that allergic skin responses are complex, often prolonged, involving several interacting cell types, with release of cell factors which are pathogenic for surrounding tissues. Findings should help our understanding of LACR and allergic inflammation.
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