Human recombinant phospholipase A2 inhibits platelet aggregation in vitro and in vivo in rat and guinea pig.
Platelets contain a phospholipase A2 in their granules which can be released in response to various activating stimuli in vitro as well as in vivo. Human recombinant phospholipase A2 (1-10 micrograms/ml) had no direct effect on platelet aggregation in vitro using rabbit platelet rich plasma. In contrast human recombinant phospholipase A2 (1-20 micrograms/ml) was able to inhibit aggregation of washed rabbit platelet in vitro induced by collagen (0.250-2.0 micrograms/ml). When rabbit platelet rich plasma was recalcified with CaCl2 1 M in the presence of the thrombin inhibitor hirulog (10 micrograms/ml), human recombinant phospholipase A2 (10-40 micrograms/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 A2 antibody. Human recombinant phospholipase A2 (1-10 micrograms) inhibited 111In-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 A2 (1-20 micrograms/ml) from Naja mocambique mocambique snake venom had no direct effect on platelet aggregation in vitro. However, Naja phospholipase A2 administered i.v. to rats or guinea pigs was able to induce a dose related accumulation of 111In-labelled platelet within the thoracic region. The inhibitory effect of exogenously added human recombinant phospholipase A2 on platelet aggregation in vivo suggests a possible pathophysiological role for the extracellular form of phospholipase A2 but this property is not a feature of all phospholipase A2 preparations.
Cirino
G
G
Department of Experimental Pharmacology, University of Naples, Italy.
Cicala
C
C
Sorrentino
R
R
Sorrentino
L
L
Browning
J L
JL
Page
C P
CP
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007205:Indium Radioisotopes; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010741:Phospholipases A / Q000276:immunology / Q000494:pharmacology*; D054467:Phospholipases A2; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D010741:Phospholipases A; D054467:Phospholipases A2