Inhibition of the activation of Hageman factor (factor XII) and of platelet aggregation by extracts of Brugia malayi microfilariae.
In human filariasis, large numbers of blood-borne microfilariae circulate unimpeded through the blood stream. How intravascular filarial parasites avoid precipitating thrombosis has not been studied in detail. We hypothesized that extracts of Brugia malayi microfilariae would contain factors that inhibit activation of hemostatic mechanisms. Initial studies demonstrated an inhibitor specific for the intrinsic coagulation cascade. The addition of microfilarial extracts to human plasma prolonged the activated partial thromboplastin time in a dose-dependent fashion but did not prolong the prothrombin, thrombin, or Russell's viper venom times. Microfilarial extracts (0.1 mg/ml) completely inhibited activation of Hageman factor (factor XII, at 0.05 U/ml) as measured in an amidolytic assay. Hageman factor previously activated by ellagic acid (factor XIIa) retained full enzymatic activity in the presence of microfilarial extract (0.1 mg/ml). The presence of inhibitory activity in the culture medium of live parasites raises the possibility that microfilariae secrete an inhibitory protein into their local environment. Microfilarial extracts at a final concentration of 0.1 mg/ml also inhibited collagen- and adenosine diphosphate-induced platelet aggregation. Arachidonic acid-induced platelet aggregation was inhibited by microfilarial extracts at a final concentration of 0.6 mg/ml. These results suggest that microfilariae of Brugia malayi, a human filarial parasite, may avoid initiating thrombosis through inhibition of the intrinsic coagulation pathway and platelet aggregation.
Foster
C B
CB
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH.
Flanigan
T P
TP
Kazura
J W
JW
Dumenco
L L
LL
Ratnoff
O D
OD
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D002009:Brugia / Q000472:pathogenicity*; D003094:Collagen / Q000494:pharmacology; D004610:Ellagic Acid / Q000494:pharmacology; D005174:Factor XII / Q000037:antagonists & inhibitors*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology
D001095:Arachidonic Acids; D010975:Platelet Aggregation Inhibitors; D004610:Ellagic Acid; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D005174:Factor XII; D003094:Collagen; D014357:Trypsin