title: Inactivation of the complement anaphylatoxin C5a by secreted products of parasitic nematodes.
abstract: Given the importance of the complement anaphylatoxins in cellular recruitment during infection, the ability of secreted products from larval stages of Brugia malayi and Trichinella spiralis to influence C5a-mediated chemotaxis of human peripheral blood granulocytes in vitro was examined. Secreted products from B. malayi microfilariae almost completely abolished chemotaxis. This inhibition was blocked by phenylmethylsulphonyl fluoride, indicating the presence of a serine protease, which was subsequently shown to cleave C5a. In contrast, secreted products from T. spiralis infective larvae showed modest inhibition of C5a-mediated granulocyte chemotaxis, and this was blocked by potato carboxypeptidase inhibitor, an inhibitor of several metallocarboxypeptidases. Adult and larval stages of both parasites were demonstrated to secrete carboxypeptidases which cleaved hippuryl-L-lysine and hippuryl-L-arginine, and the T. spiralis enzyme was partially characterised. The data are discussed with reference to inflammation in parasitic nematode infection.
authors.affiliation: Division of Cell & Molecular Biology, Department of Life Sciences, Imperial College London, London SW72AZ, UK.
authors.forename: Dominic
authors.initials: D
authors.lastname: Rees-Roberts
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mullen
authors.forename: Kleoniki
authors.initials: K
authors.lastname: Gounaris
authors.forename: Murray E
authors.initials: ME
authors.lastname: Selkirk
mesh_terms: D000706:Anaphylatoxins / Q000037:antagonists & inhibitors*; D000818:Animals; D017178:Brugia malayi / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002633:Chemotaxis / Q000276:immunology; D015936:Complement C5a / Q000037:antagonists & inhibitors*; D006790:Host-Parasite Interactions; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology; D017160:Trichinella spiralis / Q000276:immunology*
chemical_list: D000706:Anaphylatoxins; D011480:Protease Inhibitors; D015936:Complement C5a