This proposal focuses on the effects of peroxynitrite on neutrophil functions. Based on the observations by these investigators that peroxynitrite could serve a as priming agent for neutrophil functions, and that this effect may be mediated primarily by nitration of tryrosine residues on neutrophil proteins, they propose that neutrophil function is modulated during inflammation or other periods of oxidant stress by tyrosine nitration on specific neutrophil proteins. To investigate this hypothesis, they propose to 1) analyze the effects of peroxynitrite-mediated tyrosine nitration on neutrophil functional responses such as calcium flux, rolling, adhesion, chemotaxis, degranulation, phagocytosis, and cytoine production; 2) analyze the effects of peroxynitrite treatment of purified NADPH oxidase proteins on oxidase assembly and enzymatic activity in vitro; 3) identify neutrophil proteins that are modified by tyrosine nitration in intact cells by immunoprecipitation, Western blotting, and amino acid sequencing; and 4) map specific sites of nitration on neutrophil proteins using mass spectrometry, peptide mapping, and amino acid sequencing.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL066575-04
Application #
6650863
Study Section
Hematology Subcommittee 2 (HEM)
Program Officer
Harvath, Liana
Project Start
2000-09-30
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2005-08-31
Support Year
4
Fiscal Year
2003
Total Cost
$280,000
Indirect Cost
Name
Montana State University Bozeman
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
625447982
City
Bozeman
State
MT
Country
United States
Zip Code
59717
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