HUMAN RECOMBINANT NONPANCREATIC SECRETED PLATELET PHOSPHOLIPASE-A2 HAS ANTICOAGULANT ACTIVITY INVITRO ON HUMAN PLASMA

Extracellular phospholipase A2 is secreted from the platelets upon act ivation by a stimulus such as thrombin (1,2). The secreted enzyme has been recently cloned and the recombinant protein produced (2). Snake v enom PLA2 effect on platelet and coagulation has been extensively stud ied (for review see 3,4) and it has been proposed that the anticoagula nt phospholipases may inhibit coagulation by competing with clotting p roteins for the lipid surface (5). Structure function relationship for PLA2s with anticoagulant activity indicates that the activity is conf erred by positively charged aminoacids between residues 54 and 77 (6). The corresponding segment of human recombinant secreted platelet PLA2 (r-hnps-PLA2) possesses five positively charged aminoacids in this re gion being at the identical positions to those of PLA2s with known ant icoagulant activities (2). Here using human and rat plasma we have dem onstrated for the first time that the recombinant human extracellular secreted platelet PLA2 increases activated partial thromboplastin time but not prothrombin time.