# RHEUMATOID ARTHRITIS PHOSPHOLIPASES AND INFLAMMATION

> **NIH NIH R01** · ALLEGHENY UNIVERSITY OF HEALTH SCIENCES · 1988 · $65,613

## Abstract

Little is known about phospholipase activating proteins in
mammals and nothing has previously been described concerning
their role in human disease states.  The objective of this
application is to identify and isolate a phospholipase A2 activating
protein from patients with rheumatoid arthritis: to correlate the
presence of this activating protein with clinical characteristics of
rheumatoid arthritis patients compared to patients with other
forms of arthritis; to examine biochemical and cell biological
characteristics of these phospholipase A2 activating proteins; and
to begin to explore the in vivo relevance of these activators in
animal models.

Rheumatoid arthritis is an important, common and often disabling
disease of joints characterized by an extensive inflammatory
reaction.  Prostaglandins and related eicosanoids, which are
produced in enhanced quantities in this disease, help mediate this
destruction.  The rate limiting step in the eicosanoid synthesis
pathway is phospholipase enzyme cleavage of unsaturated fatty
acids such as arachidonic acid from membrane phospholipids.  We
have previously shown that cells from rheumatoid patients express
enhanced phospholipase enzyme activities compared to control
cells.  Phospholipase activating proteins such as melittin are
found in venoms from bees and snakes.  Thus, similar proteins
might be hypothesized to teleologically exist in humans.

Antimelittin antibodies will be used to immuno affinity purify a
phospholipase A2 activating protein from rheumatoid tissues, cells
and fluids.  Further purification will include HPLC gel exclusion
and SDS-PAGE.  Testing of patient specimens will be performed
by immuno dot blot and ELISA assays, as well as histochemical
localization.  The biochemical characteristics of this protein will
include its effects on phospholipase enzymes present in micelles,
liposomes, cell membranes and intact cells.  The role of parent
phospholipid substrate, sn-2 fatty acid substitution, and end
product inhibition will be explored.  The effects of this protein on
lysosomal and cytoplasmic enzyme release from monocytes and
neutrophils, and induction of eicosanoid synthesis will be
investigated.  Preliminary investigations into the in vivo
relevance of this protein in animals will include injection of this
compound into normal rabbits with quantification of the ensuing
inflammatory response, as well as observing the ontologic
development of inflammation and the presence of this
phospholipase activating protein in animal models of arthritic
inflammation.

## Key facts

- **NIH application ID:** 3159421
- **Project number:** 1R01AR039382-01
- **Recipient organization:** ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
- **Principal Investigator:** JOHN S BOMALASKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $65,613
- **Award type:** 1
- **Project period:** 1988-04-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159421

## Citation

> US National Institutes of Health, RePORTER application 3159421, RHEUMATOID ARTHRITIS PHOSPHOLIPASES AND INFLAMMATION (1R01AR039382-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159421. Licensed CC0.

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