# MECHANISMS OF TISSUE DAMAGE IN RHEUMATIC DISEASES

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 1988 · $112,291

## Abstract

The objectives of the proposed research are two-fold:  1) to study the
mechanism of induction and release of human monocyte factor (MCF, LAF, In
terleukin 1) in response to various immunological stimuli; and 2) to study
the roles of neutral proteinases activated at the plasma membrane, or
released into the cell micro-environment, in the digestion of connective
tissue substrates by human mononuclear phagocytes, fibroblasts, dendritic
cells or chondrocytes.  The hypothesis to be examined is that the
consequences of immune complex-macrophage interactions either lead to
enzymatic activation at the plasma membrane, producing damage to adjacent
tissues, or to release of soluble substances that amplify the effector
function of other cells in tissue destruction.  The methods to be used
include in-vitro systems for determining the relative effectiveness of
various forms of immune complexes in stimulating human monocytes and
macrophages to synthesize and release soluble factors (MCF) that amplify
collagenase secretion by fibroblasts, synovial dendritic cells or
chondrocytes.  These same systems also will be employed to explore the
mechanism of immune complex or Fc fragment-stimulated MCF production in
human monocytes.  In addition, ultrastructural cytochemical localization
techniques will be employed to search for the presence of active neutral
proteinases at the surface of these cells after stimulation with immune
complexes.  Other studies will utilize radiolabelled monolayers of collagen
or proteoglycans to compare the direct degradation induced by cells
cultured on these substrates with the release of specific enzymes or
inhibitors into the supernatant.

## Key facts

- **NIH application ID:** 3156315
- **Project number:** 3R01AR032470-05S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **SAM.gov UEI:** MW8JHK6ZYEX8
- **Principal Investigator:** WILLIAM P AREND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $112,291
- **Award type:** 3
- **Project period:** 1983-04-01 → 1988-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156315

## Citation

> US National Institutes of Health, RePORTER application 3156315, MECHANISMS OF TISSUE DAMAGE IN RHEUMATIC DISEASES (3R01AR032470-05S1). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156315. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*