# PATHOPHYSIOLOGY AND METABOLISM OF THE LEUKOCYTE

> **NIH NIH R01** · WAKE FOREST UNIVERSITY · 1987 · $122,516

## Abstract

This project proposes to examine stimulus-response coupling in the human
neutrophil.  The basic hypothesis is that mobilization of Ca++ is an early
event following membrane perturbation which then results in two sequellae:
the mobilization and subsequent metabolism of arachidonic acid and
activation of the respiratory burst.  The role of Ca++ will be investigated
by comparing Ca++ transport induced by various stimuli with arachidonate
metabolism and respiratory burst activity.  Specificity will be examined by
the use of calcium channel blockers and the intracellular calcium chelator,
TMB-8.  The possible role of calmodulin in these processes will be
evaluated.  Lipid metabolism in the stimulated neutrophil will be examined
using cells pre-labelled with 3H-labelled arachidonate and 14C-stearate.
Emphasis will be placed on the source and mechanism of arachidonate release
as well as its subsequent metabolism to various bioactive intermediates.
The possible relationship of the lipid alterations to the respiratory burst
will be examined by investigating the two phenomena in patients with
chronic granulomatous disease as well as by incubating normal cells with
various phospholipases and products of phospholipase metabolism.  Finally,
we are hypothesizing that the respiratory burst is mediated by a
multi-component electron transport chain.  Neutrophils (both resting and
activated) will be fractionated by previously defined techniques and
oxidase activity in each fraction (plasma membrane, specific granule, and
azurophil granule) determined by three separate assays (O2- production,
H2O2 production, and NADP formation).  These activities will be correlated
with the subcellular distribution of cytochrome b and ubiquinone.  The
kinetics of appearance of each of the above activities in the phagocytic
vacuole will be measured.  These experiments will be performed with both
cells from normal donors and from patients with chronic granulomatous
disease.  Finally, reconstitution experiments will be performed in an
attempt to activate the system in vitro by combining fractions containing
the differing activities.

## Key facts

- **NIH application ID:** 3124785
- **Project number:** 5R01AI010732-16
- **Recipient organization:** WAKE FOREST UNIVERSITY
- **SAM.gov UEI:** MBU6HCLNZ431
- **Principal Investigator:** DAVID A BASS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $122,516
- **Award type:** 5
- **Project period:** 1979-03-01 → 1988-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124785

## Citation

> US National Institutes of Health, RePORTER application 3124785, PATHOPHYSIOLOGY AND METABOLISM OF THE LEUKOCYTE (5R01AI010732-16). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124785. Licensed CC0.

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