Inhibition of the activation of Hageman factor (factor XII) by extracts of Schistosoma mansoni.
How intravascular helminth parasites evade host hemostatic defense mechanisms and survive within the circulating blood has not been adequately explained. Previous reports have described an inhibitor of the intrinsic clotting pathway in extracts of adult Schistosoma mansoni. Using a purified preparation of Hageman factor, we examined the ability of schistosome extracts and secretory products to inhibit the activation of human Hageman factor (factor XII) in an amidolytic assay. Both schistosome extracts and secretory products inhibited the activation of purified Hageman factor by more than 95%. Schistosome extracts inhibited activation of Hageman factor both by ellagic acid and by bovine sulfatides. In contrast, activated Hageman factor retained full activity in the presence of schistosome extracts as tested both on an amidolytic synthetic substrate and a natural substrate, plasma thromboplastin antecedent (factor XI). Our findings indicate that extracts and secretory products of adult Schistosoma mansoni contain a potent inhibitor of the activation of Hageman factor. Knowledge of a site at which schistosomes inhibit the intrinsic clotting pathway provides added insight into the mechanisms by which the parasites avoid the host hemostatic defense mechanisms.
Foster
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CB
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH.
Flanigan
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TP
DeStigter
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Blanton
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R
Dumenco
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LL
Gallagher
C
C
Ratnoff
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OD
D000818:Animals; D004610:Ellagic Acid / Q000494:pharmacology; D005174:Factor XII / Q000037:antagonists & inhibitors*; D015956:Factor XIIa / Q000037:antagonists & inhibitors; D012550:Schistosoma mansoni / Q000378:metabolism*; D013433:Sulfoglycosphingolipids / Q000494:pharmacology
D013433:Sulfoglycosphingolipids; D004610:Ellagic Acid; D005174:Factor XII; D015956:Factor XIIa