Crotoxin, the main toxic component isolated from the venom of the Sout
h American rattlesnake Crotalus durissus terrificus, is a reversible p
rotein complex composed of a non-toxic non-enzymatic acidic polypeptid
e (crotapotin) and a toxic basic phospholipase A(2) (PLA(2)). In this
study, we have evaluated the ability of crotoxin to induce aggregation
in human washed platelets. Human washed platelet aggregation was moni
tored in a Payton aggregometer and thromboxane B-2 (TXB(2)) release me
asured by direct radioimmunoassay (RIA). Crotoxin (15-50 mu g/ml) prod
uced dose-dependent and irreversible human washed platelet aggregation
, which was inhibited by pre-incubation of the platelets with sodium n
itroprusside (50-500 mu M) or iloprost (8-80 nM). Crotoxin also induce
d TXB, release (207 +/- 8 ng/ml, n = 6), and although indomethacin sig
nificantly reduced the release of TXB, (to 23.5 +/- 5 ng/ml, P < 0.001
, n = 6), it did not inhibit crotoxin-induced aggregation. Our results
clearly demonstrate that crotoxin induces human washed platelet aggre
gation and that this phenomenon is independent of the formation of pro
-aggregatory arachidonic acid metabolites.