Inactivation of platelet-activating factor by a putative acetylhydrolase from the gastrointestinal nematode parasite Nippostrongylus brasiliensis.
The adult stage of Nippostrongylus brasiliensis, a strongyloid parasite of the gastrointestinal tract of rats, released a product during in vitro culture which functionally inhibited platelet-activating factor (PAF), measured by its ability to mediate platelet aggregation. The extent of inhibition was proportional to the concentration of excretory/secretory (ES) products and the duration of preincubation with PAF prior to the assay of biological activity. The inhibitory activity was heat labile and was specific for PAF, as incubation of ES products with thrombin showed no diminution of platelet aggregation. Experiments using radiolabelled preparations of PAF demonstrated that the acetyl group esterified at the sn-2 position of the glycerol backbone was liberated on incubation with ES products, indicative of an acetylhydrolase activity. This activity was susceptible to inhibition by DFP, partial inhibition by eserine, but was resistant to PMSF and TPCK at concentrations which inhibit serine proteases.
Blackburn
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Wellcome Centre for Parasitic Infections, Department of Biochemistry, Imperial College of Science, Technology and Medicine, London.
Selkirk
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D000818:Animals; D004305:Dose-Response Relationship, Drug; D006867:Hydrolases / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009349:Nematode Infections / Q000276:immunology*; D009559:Nippostrongylus / Q000201:enzymology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D015842:Serine Proteinase Inhibitors; D006867:Hydrolases; D013917:Thrombin