# INFLAMMATION IN RHEUMATIC DISEASES

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1988 · $143,915

## Abstract

The long-term objective of the proposed research is to determine the roles
played by polymorphonuclear leukocytes (PMN), chemotactic factors (e.g.,
complement [C5]-derived peptides), and endothelial cells (EC) in provoking
the microvascular "injury" that accompanies immunologically-mediated, acute
inflammation in patients with rheumatic diseases.  Attempts will be made to
develop in vitro models in which we can compare adherence of PMN to blood
vessel walls under "normal" conditions and under conditions that might be
found at sites of inflammation.  Since PMN ordinarily do not adhere tightly
to endothelial surfaces in vivo, experiments will be performed to determine
factors that influence "basal" adherence of human PMN to cultured human
EC.  Specific attention will be directed at chemotactic factor-induced
adhesive interactions between PMN and EC.  Results of our preliminary
studies suggest that chemotactic factors not only increase the number of
PMN that adhere to EC, but also increase the strength of adherence by
increasing expression on the surface of PMN of a glycoprotein complex
recognized by monoclonal antibody 60.3.  Studies are planned to elucidate
further the mechanism(s) by which chemotactic factors alter the
adhesiveness of PMN.  The hypothesis will be tested that lectin-like
glycoprotein complex (recognized by 60.3) mediates attachment of PMN to EC,
and that this complex is translocated from tertiary granules to the cell
surface upon exposure of PMN to chemotactic factors.  Finally, studies are
planned to examine whether PMN interact differently with microvascular EC
than with EC from large blood vessels.  Since we have been able to maintain
in culture EC derived from human umbilical veins and from the microvessels
of human skin, it should be possible to test the hypothesis that
microvascular EC possess unique properties which render them more
susceptible than EC from large blood vessels to PMN-induced "injury".
These studies should provide significant new information concerning the
roles played by PMN, EC and C5-derived peptides in the pathogenesis of
acute, immunologically-mediated inflammation.

## Key facts

- **NIH application ID:** 3157824
- **Project number:** 5R01AR036949-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** IRA M. GOLDSTEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $143,915
- **Award type:** 5
- **Project period:** 1986-04-01 → 1989-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157824

## Citation

> US National Institutes of Health, RePORTER application 3157824, INFLAMMATION IN RHEUMATIC DISEASES (5R01AR036949-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3157824. Licensed CC0.

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