Adhesive receptor Mac-1 coordinates the activation of factor X on stimulated cells of monocytic and myeloid differentiation: An alternative initiation of the coagulation protease cascade

D. C. Altieri, James H Morrissey, T. S. Edgington

Research output: Contribution to journalArticle

Abstract

Monocytes initiate coagulation through regulated surface expression of tissue factor and local assembly of a proteolytic enzymatic complex formed by tissue factor and factor VII/activated factor VII. We now show that, in the absence of these initiating molecules, monocytes and cell lines of monocytic/myeloid differentiation can alternatively initiate coagulation after exposure to ADP. The molecular basis for this procoagulant response consists of two distinct events. First, cell stimulation with ADP induces high-affinity binding of coagulation factor X to the surface-adhesive receptor Mac-1. Locally, Mac-1-concentrated factor X is then rapidly proteolytically cleaved to an active protease with size and activity characteristics of activated factor X, which supports the cell-associated formation of thrombin and the procoagulant response. We conclude that the monocytic/myeloid adhesive receptor Mac-1 has the unexpected, specifically inducible property to organize a molecular assembly culminating in rapid fibrin formation that is independently regulated from tissue factor and factor VII/activated factor VII.

Original languageEnglish (US)
Pages (from-to)7462-7466
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number20
DOIs
StatePublished - Jan 1 1988

ASJC Scopus subject areas

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