# PRIMING & STIMULATION OF GRANULOCYTES

> **NIH NIH R01** · WAKE FOREST UNIVERSITY · 1988 · $133,688

## Abstract

"Priming" of granulocytes (PMNL) signifies an increased
responsiveness to stimulation in vitro.  The respiratory burst is
important to the bactericidal activity of PMNL and priming of the
burst may be an important aspect of host defense in such patients.
Normal PMNL can be primed in vitro by preincubation with certain
agonists, followed by stimulation with a second agonist.  We
hypothesize that priming involves synergistic convergence of
separate, collateral stimulus-response coupling mechanisms.  Since
it is effective for over 10 minutes, priming can be used to dissect
transductional mechanisms into sequential events.  This facilitates
analysis of causal relationships among the many "early events"
occurring after stimulation of membrane receptors.

1,2-diacylglycerols prime both initiation (lag time, initial rate)
and duration of the burst stimulated by formyl-met-leu-phe or by
phagocytosis.  1-0-alkyl-2-acylglycerols prime only initiation.
Thus, initial activation of the NADPH oxidase and the maintenance
of ongoing oxidase activation are separable and will be probed with
this model system.

Priming and primed stimulation are hypothesized to involve
interactions between 1) diglycerides, 2) arachidonic acid (AA)
release and metabolism, 3) altered membrane structure, 4) synergy
between DGs and/or AA with Ca++ in activation of Ca++  -dependent
enzymes.  These synergistic mechanisms are proposed to cause 5)
structural modification (e.g., protein phosphorylation) and 6)
translocation to the plasma membrane of intracellular components
with assembly and activation of the NADPH oxidase.  The project is
therefore divided into 6 specific aims as follows:

1)  Using synthetic diglyceride analogs, define the molecular
specificity for priming of initiation and prolongation of the
burst.  Use these models in aims 2-6.  2) Determine the role of
PLA2 activation by direct measurement of AA release and metabolism;
determine that primed-stimulation also involves increased
sensitivity to AA-mediated events.  3) Determine physical membrane
changes induced by priming and primed stimulation using several
fluorescent and resonance methods.  4) Determine changes in
cytosolic (Ca++), 45Ca fluxes, and the effects of chelation of
intracellular Ca on each of the parameters.  5) Define protein
phosphorylation occurring with priming and primed stimulation.  6)
Define translocation of oxidase components, oxidase kinetics and
changes in concentration of the oxidase substrate, NADPH, in each
model system.

## Key facts

- **NIH application ID:** 3125928
- **Project number:** 2R01AI014929-09
- **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:** 1988
- **Award amount:** $133,688
- **Award type:** 2
- **Project period:** 1979-09-01 → 1992-11-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125928

## Citation

> US National Institutes of Health, RePORTER application 3125928, PRIMING & STIMULATION OF GRANULOCYTES (2R01AI014929-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125928. Licensed CC0.

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