Sequential receptor cascade for coagulation proteins on monocytes. Constitutive biosynthesis and functional prothrombinase activity of a membrane form of factor V/Va.
Cells of monocytic differentiation can promote proteolytic activation of factor X following binding to the adhesive receptor Mac-1. We now show that the product, factor Xa, binds to a second receptor on these cells in a Ca2+-dependent reaction. Functionally, this results in the capacity to convert prothrombin to thrombin. The factor Xa receptor was identified by monoclonal antibody (7G12) reactive with plasma factor V/Va, but selected for reactivity with THP-1 cells. It reacted with 71.2 +/- 10.1% of monocytes, bound 153,600 +/- 33,500 sites/THP-1 cell, blocked binding of 125I-factor Xa, inhibited formation of thrombin, and immunoprecipitated 125I-factor Xa chemically cross-linked to its receptor on THP-1 cells. Following surface iodination or intrinsic labeling of THP-1 cells, antibody 7G12 immunoprecipitated a 74-kDa molecular species, similar to plasma factor Va light chain. Thus, monocytes and monocyte-like cells synthesize and express a factor V/Va-like receptor for factor Xa and organize a functional prothrombinase complex. The simultaneous membrane coexpression of a factor X receptor (Mac-1) and a factor Xa receptor as demonstrated by two-color flow cytofluorometric analysis of monocytes or THP-1 cells is consistent with a sequential receptor cascade for coordinated molecular assembly of coagulation proteins on specialized cells.
Altieri
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Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Edgington
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TS
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005165:Factor V / Q000096:biosynthesis / Q000378:metabolism*; D015943:Factor Va; D015951:Factor Xa; D006801:Humans; D007700:Kinetics; D009000:Monocytes / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; C045069:factor X receptors; D015943:Factor Va; D005165:Factor V; D012697:Serine Endopeptidases; D015951:Factor Xa