INHIBITION OF CARRAGEENAN-INDUCED RAT PAW EDEMA BY CROTAPOTIN, A POLYPEPTIDE COMPLEXED WITH PHOSPHOLIPASE A(2)

1 The effect of purified crotapotin, a non-toxic non-enzymatic chapero n protein normally complexed to a phospholipase A(2) (PLA(2)) in South America rattlesnake venom, was studied in the acute inflammatory resp onse induced by carrageenin (1 mg/paw), compound 48/80 (3 mu g/paw) an d 5-hydroxytryptamine (5-HT) (3 mu g/paw) in the rat hind-paw. The eff ects of crotapotin on platelet aggregation, mast cell degranulation an d eicosanoid release from guinea-pig isolated lung were also investiga ted. 2 Subplantar co-injection of crotapotin (1 and 10 mu g/paw) with carrageenin or injection of crotapotin (10 mu g/paw) into the contrala teral paw significantly inhibited the carrageenin-induced oedema. This inhibition was also observed when crotapotin (10-30 mu g/paw) was adm inistered either intraperitoneally or orally. Subplantar injection of heated crotapotin (15 min at 60 degrees C) failed to inhibit carrageen in-induced oedema. Subplantar injection of crotapotin (10 mu g/paw) al so significantly inhibited the rat paw oedema induced by compound 48/8 0, but it did not affect 5-HT-induced oedema. 3 In adrenalectomized an imals, subplantar injection of crotapotin markedly inhibited the oedem a induced by carrageenin. The inhibitory effect of crotapotin was also observed in rats depleted of histamine and 5-HT stores. 4 Crotapotin (30 mu g/paw) had no effect on either the histamine release induced by compound 48/80 in vitro or on the platelet aggregation induced by bot h arachidonic acid (1 mM) and platelet activating factor (1 mu M) in h uman platelet-rich plasma. The platelet aggregation and thromboxane B- 2 (TXB(2)) release induced by thrombin (100 mu ml(-1)) in washed human platelets were also not affected by crotapotin. In addition, crotapot in (10 mu g/paw) did not affect the release of 6-oxo-prostaglandin F1 alpha and TXB(2) induced by ovalbumin in sensitized guinea-pig isolate d lungs. 5 Our results indicate that the anti-inflammatory activity of crotapotin is not due to endogenous corticosteroid release or inhibit ion of cyclo-oxygenase activity. It is possible that crotapotin may in teract with extracellular PLA(2) generated during the inflammatory pro cess thereby reducing its hydrolytic activity.