Human granulocytes play a pivotal role in mediating tissue damage in a variety of inflammatory disease states. In order to gain further insight into the pathogenesis of tissue injury during inflammation, our attention will focus on the ability of two populations of phagocytes, neutrophils and eosinophils, to generate oxygen metabolites by peroxidase-dependent processes and to use these oxidants to mediate pro-inflammatory effects. Specific emphasis will be placed on assessing the function of the bromide oxidation product, hypobromous acid, in the human eosinophil and contrasting its role to that of hypochlorous acid in the neutrophil. In addition, myeloperoxidase-deficient neutrophils will be employed to probe potential roles for oxygen-derived, peroxidase-independent metabolities as inflammatory mediators. The significance of these in vitro events will then be extended to a physiologic setting by examining the ability of neutrophils and eosinophils to generate and use halogenated oxidants in plasma- supplemented model systems. Finally, this information will be used to design monitoring systems able to detect and quantitate the predicted generation of halogenated oxidants at inflamed sites in vivo. Taken together, these studies will provide new insights into the role of granulocyte-derived oxidants in the pathogenesis of inflammation at the cellular and molecular level both in vitro and in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI021301-05
Application #
3131265
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1984-07-01
Project End
1992-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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