This proposal is divided into (1) study of the contribution of mast cell and eosinophil-dependent pathways to the pathogenesis of the human cutaneous blistering disorder bullous pemphigoid, and (2) isolation, characterization, and development of specific assays for components of the human neutrophil neutral peptide generating pathway, so as to permit study of this pathway in appropriate human cutaneous disorders. Neutrophil, eosinophil and lymphocyte chemotactic factors from bullous pemphigoid blister fluid will be purified and characterized so that their targets in human skin and their cell of origin may be determined. The cellular and humoral contribution to the regulation of histamine in bullous pemphigoid blister fluid will be studied. The chemical data will be correlated with the order of pathologic alterations as determined by electron microscopic and histopathologic study of developing skin lesions. Components of the neutrophil pathway for the generation of a neutral peptide mediator and the degradation of fibrinogen and fibrin will be fully characterized. The neutral peptide product will be purified, characterized, structurally defined and synthesized in vitro. The biology of components of this pathway will be studied and specific immunoassays will be developed for quantitation of each component in complex biologic fluids and detection in tissue.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
2R01AM031901-03
Application #
3152374
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1982-07-01
Project End
1987-12-31
Budget Start
1985-04-01
Budget End
1985-12-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Vanderslice, P; Ballinger, S M; Tam, E K et al. (1990) Human mast cell tryptase: multiple cDNAs and genes reveal a multigene serine protease family. Proc Natl Acad Sci U S A 87:3811-5
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Weiss, T L; Barker, M E; Selleck, S E et al. (1989) Erythropoietin binding and induced differentiation of Rauscher erythroleukemia cell line red 5-1.5. J Biol Chem 264:1804-10
Goldstein, S M; Kaempfer, C E; Kealey, J T et al. (1989) Human mast cell carboxypeptidase. Purification and characterization. J Clin Invest 83:1630-6
Goldstein, S M; Kaempfer, C E; Proud, D et al. (1987) Detection and partial characterization of a human mast cell carboxypeptidase. J Immunol 139:2724-9
Snyder, R A; Wintroub, B U (1986) Inhibition of angiotensin-converting enzyme by des-Leu10-angiotensin I: a potential mechanism of endogenous angiotensin-converting enzyme regulation. Biochim Biophys Acta 871:1-5

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