# MOLECULAR MECHANISMS OF NEUTROPHIL SUPEROXIDE GENERATION

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 1988 · $138,757

## Abstract

The goals of the proposed program are a comprehensive analysis of the
cellular and biochemical mechanisms of the conversion of oxygen to
superoxide (02.-) and other high reactive radicals by human PMN leukocytes,
an examination of the activation and modulation of these oxidative pathways
by highly purified or synthetic mediators of the leukocyte component of
immunological responses, and the definition of the roles of the oxygen
metabolites of PMN leukocytes in host defense and in the tissue destruction
associated with some inflammatory reactions.  The NADPH-dependent (02.-)
generating activity of human PMN leukocytes will be purified to a state of
homogeneity in order to permit studies of the enzymatic mechanisms of
(02.-) formation.  A unique cytochrome b of PMN leukocytes, that has been
implicated in (02.-) generation, will be isolated to elucidate its role as
a co-factor.  Antibodies will be prepared to both the highly purified
NADPH-dependent (02.-) generating oxidase and the b type cytochrome to
assess the functional role of each component, the process of activation,
and the subcellular localization of the (02.-) generating activity in
intact PMN leukocytes.  Biochemical and immunochemical techniques will be
applied to the identification of distinct deficiencies in the oxidative
pathways of PMN leukocytes which fail to exhibit a respiratory burst of
normal magnitude.  As autoinactivation of the NADPH-oxidase of human PMN
leukocytes is a mechanism for the control of the production of (02.-), one
facet of the program will consist of a biochemical analysis of the
inactivation process.  Since the interaction of human PMN leukocytes with
defined immunological mediators of cellular function enhances the
production of (02.-), the biochemical sequence that links specific
receptors for the mediators to oxygen metabolism will be examined utilizing
several classes of agonists and inhibitors.

## Key facts

- **NIH application ID:** 3129568
- **Project number:** 5R01AI020064-07
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **SAM.gov UEI:** FBYMGMHW4X95
- **Principal Investigator:** ALFRED I TAUBER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $138,757
- **Award type:** 5
- **Project period:** 1982-08-01 → 1989-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129568

## Citation

> US National Institutes of Health, RePORTER application 3129568, MOLECULAR MECHANISMS OF NEUTROPHIL SUPEROXIDE GENERATION (5R01AI020064-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129568. Licensed CC0.

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