Our hypothesis is that interleukin-1 (IL-1) induced neutrophil recruitment and activation with release of damaging oxygen radicals (02*) and/or elastase is a fundamental feature of ARDS. We propose that endotoxin (LPS) and IL-1 initiate neutrophil recruitment and activation by production of LTB4, IL-8 and increased xanthine oxidase (XO) activity leading to superoxide (O2) activated chemotaxins. Activated neutrophils inflict oxidative damage reflected by glutathione oxidation, antiprotease inactivation, vitamin E depletion and lipid peroxidation. These events cause acute lung injury, kidney damage, more neutrophil influx and lacerations in neutrophils. Concomitant increases in markers (MnSOD, catalase, GSSG, MPO, elastase-alpha1Pi complexes, and H202 and other factors) reflect and impact ARDS progression.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL040784-09
Application #
2028390
Study Section
Special Emphasis Panel (ZHL1-CSR-B (M2))
Project Start
1988-12-01
Project End
1998-11-30
Budget Start
1996-12-01
Budget End
1997-11-30
Support Year
9
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
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