# FUNCTIONAL AND METABOLIC PROPERTIES OF TOXIC NEUTROPHILS

> **NIH NIH R01** · WAKE FOREST UNIVERSITY · 1987 · $191,444

## Abstract

Quantitation of characteristics of polymorphonuclear leukocytes (PMNL) from
patients with acute bacterial infections (ABI) has been limited in that
standard assays measure mean activity of a bulk cell population.  Such
studies have suggested variable alterations in toxic PMNL; PMNL from most
patients demonstrated augmented ("activated") responses, but some patient's
PMNL had decreased responses to stimulation in vitro.  The variability of
the previous data is probably due to 1) toxic PMNL comprise a
quantitatively variable subpopulation of circulating PMNL in patients with
ABI, 2) even among the toxic PMNL subpopulation, these cells may differ in
their degree of "toxicity", extending from activated to deactivated.  We
will employ a new, quantitative, biochemically defined flow cytometric
assay to monitor oxidative product formation by normal PMNL, PMNL from
patients with ABI and from patients with other causes of neutrophil
leukocytosis, to define the presence of PMNL subpopulatins of varying
oxidative metabolic capability.  We will also examine the cellular
mechanisms which hypothetically couple membrane stimulation to functional
responses, e.g., transmembrane potential depolarization and increased
cytosolic free Ca++ concentration.  Using dual beam fluorescence flow
cytometry, we will perform correlative analysis of any two of these
variables at the same time within individual cells, to ascertain
relationships between these putatively casually related events in
stimulated normal and toxic PMNL.  This should define the
functional/biochemical alterations of toxic PMNL with a precision
previously not attainable.  With this definition of the alterations of
toxic PMNL, especially those with augmented (activated) responsiveness in
vitro, we will examine whether defined humoral agents caused similar
activation of normal PMNL during co-incubation in vitro.  Agents to be
examined will include highly purified chemotactic factors (C5a,
N-formyl-methionyl peptides), substances released by stimulated neutrophils
(in particular hydroxylated derivatives of arachidonic acid and platelet
activating factor), and substances released during acute inflammation by
mononuclear cells (in particular interleukin 1 and colony stimulating
factor).  The ability of these substances to alter each step in the
stimulus-response coupling sequence will be quantitatively analyzed.

## Key facts

- **NIH application ID:** 3124519
- **Project number:** 5R01AI009169-15
- **Recipient organization:** WAKE FOREST UNIVERSITY
- **SAM.gov UEI:** MBU6HCLNZ431
- **Principal Investigator:** Charles Emory McCall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $191,444
- **Award type:** 5
- **Project period:** 1974-04-01 → 1988-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124519

## Citation

> US National Institutes of Health, RePORTER application 3124519, FUNCTIONAL AND METABOLIC PROPERTIES OF TOXIC NEUTROPHILS (5R01AI009169-15). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124519. Licensed CC0.

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