# STIMULATION OF NEUTROPHIL ARACHIDONATE METABOLISM

> **NIH NIH R01** · WAKE FOREST UNIVERSITY · 1988 · $140,340

## Abstract

Arachidonic acid (AA) is the precursor of an array of potent
oxidation products (eicosanoids) whose role in inflammation and
hypersensitivity reactions is widely recognized.  The AA is bound
in the 2-position of membrane phospholipids and must be released
before conversion to eicosanoids.  In PMN phospholipase A2 appears
to be the major enzyme responsible for release of the AA and the
choline-containing phosphoglycerides (PC) appear to be a major
donor of AA.  Earlier studies revealed that the PC of human PMN is
comprised of 46% alkyl ether-linked species enriched in AA.
Further studies demonstrated that l-0-alkyl-2-AA-sn-glycero-3-
phosphocholine (l-0-alkyl-2-AA-GPC) can serve as a precursor of
both eicosanoids and platelet activating factor (PAF), another
powerful mediator of PMN function.  A series of studies have
indicated that the eicosanoids and PAF act in concert to elicit
activity.  The PC was also recently shown to yield alkyl-ether-
linked diglycerides (DG) upon stimulation, possibly providing an
alternate route to the phosphatidylinositol cycle for production
of second messenger DG.  The alkyl-DG was found to potentiate the
activity of other agonists in the activation of PMN but differed
in its effects from those of diacyl-DG.  The alkyl-DG may be able
to terminate responses elicited through protein kinase C
activation.  The formation of products from l-0-alkyl-2-AA-GPC will
be investigated in PMN by prelabeling the membrane lipids with
labeled l-0-alkyl-2-AA-GPC and studying the conversion to products
in both whole cells and cell-free systems.  A goal of the study is
to characterize the phospholipase A2 responsible for the release
of AA, and the phospholipase responsible for the formation of DG
from PC.  Another goal is to determine the subcellular distribution
of AA and the molecular species distribution of AA in various
subcellular organelles and to identify the specific donor(s) of AA
in stimulated PMN.  A highly specific CoA-independent transacylase
acylates l-0-alkyl-2-lyso-GPC with AA.  This transacylase is to be
further characterized.  In PMN obtained from monkeys maintained on
a fish oil-enriched diet, a dramatic shift in the pattern of
acylation of l-0-alkyl-2-lyso-GPC was observed; the major product
formed contained eicosapentaenoic acid (EPA) rather than AA.
Beneficial effects on cardiovascular and inflammatory disorders
have been attributed to EPA.  In the proposed studies the possible
influence of EPA-containing phospholipids on the interrelationships
of AA and PAF metabolism will be explored.

## Key facts

- **NIH application ID:** 3127105
- **Project number:** 2R01AI017287-07
- **Recipient organization:** WAKE FOREST UNIVERSITY
- **SAM.gov UEI:** MBU6HCLNZ431
- **Principal Investigator:** ROBERT L WYKLE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $140,340
- **Award type:** 2
- **Project period:** 1981-09-30 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127105

## Citation

> US National Institutes of Health, RePORTER application 3127105, STIMULATION OF NEUTROPHIL ARACHIDONATE METABOLISM (2R01AI017287-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127105. Licensed CC0.

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