HUMAN RECOMBINANT PHOSPHOLIPASE A(2) INHIBITS PLATELET-AGGREGATION IN-VITRO AND IN-VIVO IN RAT AND GUINEA-PIG

Platelets contain a phospholipase A(2) in their granules which can be released in response to various activating stimuli in vitro as well as in vivo. Human recombinant phospholipase A(2) (1-10 mu g/ml) had no direct effect on platelet aggregation in vitro using rabbit platelet rich plasma. In contrast human recombinant phospholipase A(2) (1-20 mu g/ml) was able to inhibit aggregation of washed rabbit platelet in vitro induced by collagen (0.250-2.0 mu g/ml). When rabbit platelet rich plasma was recalcified with CaCl2, 1 M in the presence of the thrombin inhibitor hirulog (10 mu g/ml), human recombinant phospholipase A(2) (10-40 mu g/ml) was able to inhibit platelet aggregation. The anti-aggregatory effect was removed by incubation of platelet rich plasma with a monoclonal anti-human recombinant phospholipase A(2) antibody. Human recombinant phospholipase A(2) (1-10 mu g) inhibited In-111-labelled platelet accumulation within the thoracic region of rats and guinea pigs induced by i.v. administration of submaximal doses of collagen or adenosine diphosphate. Phospholipase A(2) (1-20 mu g/ml) from Naja mocambique mocambique snake venom had no direct effect on platelet aggregation in vitro. However, Naja phospholipase A(2) administered i.v. to rats or guinea pigs was able to induce a dose related accumulation of In-111-labelled platelet within the thoracic region. The inhibitory effect of exogenously added human recombinant phospholipase A(2) on platelet aggregation in vivo suggests a possible pathophysiological role for the extracellular form of phospholipase A, but this property is not a feature of all phospholipase A(2) preparations.