# FUNCTIONAL AND METABOLIC PROPERTIES OF TOXIC NEUTROPHILS

> **NIH NIH R01** · WAKE FOREST UNIVERSITY · 1988 · $224,740

## Abstract

Polymorphonuclear leukocytes (PMN) which are "primed" have enhanced
responsiveness to stimulation in vitro.  Priming of PMN responses
(respiratory burst or degranulation) can be induced in vitro, and
occurs in vivo in PMN obtained from patients with diseases
associated with myeloid stimulation (e.g. bacteremia).  Increases
in the defensive or injurious potential of PMN exist in primed PMN.
We have recently delineated a novel transductional sequence in
human PMN which may be important in priming.  It involves
hydrolysis of choline-containing-phospholipids (PC) with
accumulation of l-acyl-2-acylglycerol (AAG) and l-alkyl-2-
acylglycerol (EAG) and their respective phosphatidic acids (AAPA
& EAPA). We also have determined that AAG and EAG have distinct
biological activities.  Other preliminary studies in our
laboratories show constitutive expression of specific genes of PMN
in the basal state, and inducible regulation of certain genes
during priming in vitro and in vivo (e.g. c-fos and IL-1 alpha).
Our two aims pertain to these recent observations.

In Aim 1 we will test the hypothesis that diglycerides AAG and EAG
or phosphatidic acids AAPA or EAPA which accumulate after PC
hydrolysis play an important role in priming PMN.  Under defined
conditions of priming (immediate or delayed, transient or prolonged
priming in vitro, and priming in vivo), we will analyze
accumulation of radiolabelled AAG, EAG, AAPA, EAPA after hydrolysis
of PC, as well as changes in mass of species and subspecies of
these four products. Thereafter, we will test the ability of
structurally-specific subspecies of AAG, EAG, AAPA, EAPA to prime
PMN in vitro.  Finally, we will elucidate in a cell-free system the
enzymes required for production of diglycerides and phosphatidic
acids from PC.

In Aim 2 we first will extend our studies on basal expression of
PMN genes.  Second we will test the hypothesis that delayed priming
in vitro and priming in vivo are associated with specific
alterations in transcriptional and translational events. Genes
coding for three categories of proteins will be evaluated:  known
functional proteins (e.g. cytochrome B 559); putative regulatory
proteins (e.g. protein kinases C); secreted proinflammatory
proteins interleukin 1).  Third, we will evaluate transductional
stimuli which may modify gene expression in PMN, particularly AAG,
EAG, AAPA, EAPA.

## Key facts

- **NIH application ID:** 3124515
- **Project number:** 2R01AI009169-16
- **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:** 1988
- **Award amount:** $224,740
- **Award type:** 2
- **Project period:** 1974-04-01 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124515

## Citation

> US National Institutes of Health, RePORTER application 3124515, FUNCTIONAL AND METABOLIC PROPERTIES OF TOXIC NEUTROPHILS (2R01AI009169-16). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124515. Licensed CC0.

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