Abstract

Entering its second decade, this program represents a systematic approach to the study of leukocyte chemotaxis with an emphasis on the biological functions of C5-related chemotactic peptides. Fragmentation products from 14C-C5 will be defined by physical-chemical parameters using convertases from a variety of sources. We will also investigate the nature of the inactivation products from C5a produced by the chemotactic factor inactivator. The other thrust of this study is to determine the pathogenesis of immune complex-induced tissue injury. An in vitro protease assay will be employed using both solid phase and fluid phase systems. Rat leukocytic proteases will be defined according to susceptibility to inhibitors which will then be used in conjunction with superoxide dimutase to determine if in vitro substrate hydrolysis and in vivo tissue injury can be averted by these inhibitors present alone or in combination.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL028442-05
Application #
3339801
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1981-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Mulligan, M S; Ward, P A (1992) Immune complex-induced lung and dermal vascular injury. Differing requirements for tumor necrosis factor-alpha and IL-1. J Immunol 149:331-9
Yu, G H; Tarapchak, S J; Walker, B A et al. (1991) Adenosine-5'-O-(3-thiotriphosphate) binding to human neutrophils. Evidence for a common nucleotide receptor. Lab Invest 65:316-23
Walker, B A; Hagenlocker, B E; Douglas, V K et al. (1991) Nucleotide responses of human neutrophils. Lab Invest 64:105-12
Hagenlocker, B E; Walker, B A; Ward, P A (1990) Superoxide responses of immune complex-stimulated rat alveolar macrophages. Intracellular calcium and priming. J Immunol 144:3898-906
Warren, J S; Johnson, K J; Ward, P A (1990) PAF and immune complex-induced injury. J Lipid Mediat 2 Suppl:S229-37
Warren, J S; Yabroff, K R; Mandel, D M et al. (1990) Role of O2- in neutrophil recruitment into sites of dermal and pulmonary vasculitis. Free Radic Biol Med 8:163-72
Ginsburg, I (1989) Bacteriolysis is inhibited by hydrogen peroxide and by proteases. Agents Actions 28:238-42
Ward, P A; Warren, J S; Till, G O et al. (1989) Modification of disease by preventing free radical formation: a new concept in pharmacological intervention. Baillieres Clin Haematol 2:391-402
Schuger, L; Varani, J; Marks, R M et al. (1989) Cytotoxicity of tumor necrosis factor-alpha for human umbilical vein endothelial cells. Lab Invest 61:62-8
Gibbs, D; Varani, J; Ginsburg, I (1989) Formation and use of poly-L-histidine-catalase complexes: protection of cells from hydrogen peroxide-mediated injury. Inflammation 13:465-74

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