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.
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.
Altieri
D C
DC
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Morrissey
J H
JH
Edgington
T S
TS
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001777:Blood Coagulation; D001853:Bone Marrow / Q000201:enzymology / Q000378:metabolism*; D001854:Bone Marrow Cells; D002460:Cell Line; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005167:Factor VII / Q000378:metabolism; D005170:Factor X / Q000378:metabolism*; D015951:Factor Xa; D005434:Flow Cytometry; D006801:Humans; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011951:Receptors, Complement / Q000378:metabolism*; D017463:Receptors, Complement 3b; D012697:Serine Endopeptidases / Q000378:metabolism; D013925:Thromboplastin / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D000244:Adenosine Diphosphate; D005167:Factor VII; D005170:Factor X; D013925:Thromboplastin; D010447:Peptide Hydrolases; D012697:Serine Endopeptidases; D015951:Factor Xa