# HUMAN MONOCYTE MODULATION OF COAGULATION/FIBRINOLYSIS

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 1988 · $66,478

## Abstract

Both fibrin and monocytes are present in lesions of immune mediated tissue
damage.  The process of fibrin deposition in these lesions may involve
monocytes, as these cells respond to many inflammatory stimuli by
elaborating potent procoagulant activity (PCA).  Indeed, expression of
monocyte PCA seems to be an intrinsic part of the immune response as
T-lymphocytes are required for recognition of specific stimuli, with
subsequent instructions to monocytes.  There are also processes which
control the persistence of fibrin as it is formed.  Monocytes secrete an
inhibitor of urokinase (UK-I) which would serve to impede fibrinolysis.
Monocyte secretion of UK-I is augmented by exposure to inflammatory
stimuli.  It is therefore possible that local expression of monocyte PCA
and UK-I are important in the pathogenesis of certain lesions.  Indeed,
there is an increased incidence of occlusive vascular events in diseases
marked by conditions which increase monocyte PCA in vitro.  However,
monocytes also secrete prourokinase (pro UK).  Pro UK derived from non
monocyte sources may have plasminogen activator activity.  It is not known
if monocyte secretion of pro Uk is influenced by inflammatory stimuli.  The
balance between the above activities would therefore be important.  The
studies outlined herein propose to use methods operative in our lab or
published in the literature to:  i) determine whether synthesis and
secretion of pro UK by human monocytes is influenced by inflammatory
stimuli (assay by quantitative Western blotting, use of 3H-Leucine to
discern changes due to synthesis vs secretion of preformed pro UK); ii)
determine cellular interactions and metabolic requirements of lymphocyte
and monocyte populations in modulation of procoagulant, profibrinolytic,
and fibrinolytic inhibitory molecules (using T-cell clones, isolated
monocytes and specific assays for each activity); iii) determine
relationships in regulation of procoagulant, profibrinolytic, and
fibrinolytic inhibitor activities, i.e., how is the "balance" regulated?
(Derived from data of the above experiments); iv) determine whether
prourokinase elaborated by monocytes is fibrinolytically active or a
pro-enzyme (direct measurement of cleavage of 125I plasminogen to avoid
confounding effects of plasmin activation of pro UK to UK.  Western
blotting of reaction mixtures to identify active (pro) UK as 1 or 2
chains); and v) determine the effects of binding of urokinase by monocytes
on its biologic activity (efficiency as a plasminogen activator, and
susceptibility to UK-I).

## Key facts

- **NIH application ID:** 3129790
- **Project number:** 5R01AI020247-06
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **SAM.gov UEI:** LCLSJAGTNZQ7
- **Principal Investigator:** BRADFORD S SCHWARTZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $66,478
- **Award type:** 5
- **Project period:** 1983-08-01 → 1989-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129790

## Citation

> US National Institutes of Health, RePORTER application 3129790, HUMAN MONOCYTE MODULATION OF COAGULATION/FIBRINOLYSIS (5R01AI020247-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129790. Licensed CC0.

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