# NEUTROPHIL FUNCTION AND AGING

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 1992 · $169,416

## Abstract

DESCRIPTION (adapted from the applicant's abstract):  This is a revised
proposal for five years of funding for the support of studies in the
age-associated defect of neutrophil function in man.  The Investigator
proposes to continue with studies based on observations he and his
coworkers have already made.  The fundamental theme is the utilization of
the neutrophil as a model of cellular aging, with the expectation that
mechanistic studies of a defect in the function of "aged" neutrophils,
previously reported and studied by the Investigator, will lead to an
understanding of the widespread and various defects in cellular function
which accompany aging.

The experiments are planned around four specific aims:  1) to define the
age-related decline in signal transduction, 2) to explain why the
age-related decrements in signal transduction are greater at early steps in
the pathway than later events, 3) to define whether the age-related decline
in function is heterogeneous among neutrophils, and 4) to identify the
reversible change in the cell membrane that accounts for the age-related
decrease in receptor-mediated responses.

Further studies of the turnover of phosphoinositide precursors of DAG and
IP3 were planned, and considerable progress has already been made with
this, as described in the supplemental material.  Also planned are studies
of the number of high and low-affinity fMLP receptors of young and old
cells.  Studies of the effect of age on G protein regulation of receptor
kinetics will concentrate on Gn, a CT binding protein thought to play a
role in transducing the signal from the fMLP receptor to PLC.  Experiments
will be based on the concept that Gn is dissociated into three subunits on
activation by flvILP, and that subsequently ribolsylated.  The method for
quantifying the GTP-ase activity will be measured by assessing the
liberation of radioactive phosphorous from labeled GTP.  ability of PT to
catalyze ADP-ribosylation of the alpha subunit was described by Bokoch, who
will act as a collaborator in the proposed studies.  He has also developed
immunoblot assays for the subunits1 and the Investigator includes a letter
promising Dr. Bokoch's collaboration.  Studies of the activity of PLC, PLD
and PLA2 activity will also be carried out.

Now in other studies, FACS will be used to assess membrane
potential(di-1-C5(3)), formation of oxidative products (DCF), the
mobilization of calcium (indo-1 AM) -and the binding of fluorescenated
flVILF.  An expert collaborator, Dr. Epstein at the University of Arkansas,
will aid with this.  Finally, membrane microviscosity will be estimated
using the fluorescent probes, DPH, PRO-DPH, A-DPH, cis-parinarate and
para-parinarate.  Dr. Mrak will aid with this.

## Key facts

- **NIH application ID:** 3121319
- **Project number:** 5R01AG009458-02
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **SAM.gov UEI:** VDFYLZPJEAV6
- **Principal Investigator:** David A Lipschitz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $169,416
- **Award type:** 5
- **Project period:** 1991-09-01 → 1996-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121319

## Citation

> US National Institutes of Health, RePORTER application 3121319, NEUTROPHIL FUNCTION AND AGING (5R01AG009458-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121319. Licensed CC0.

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