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ARS Home » Research » Publications at this Location » Publication #105955
Title: TRICHURIS SUIS: A SECRETORY CHYMOTRYPSIN/ELASTASE INHIBITOR WITH POTENTIAL AS A IMMUNOMODULATOR

Author
item Rhoads, Marcia
item Fetterer, Raymond
item Hill, Dolores
item Urban, Joseph

Submitted to: Molecular and Biochemical Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/12/1999
Publication Date: 5/1/2000
Citation: Rhoads, M.L., Fetterer, R.H., Hill, D.E., Urban Jr, J.F. 2000. Trichuris suis: a secretory chymotrypsin/elastase inhibitor with potential as a immunomodulator. Molecular and Biochemical Parasitology. 95:36-44 (2000)

Interpretive Summary: Worms that infect livestock cause disease and economic losses estimated at over 200 million dollars annually. The effectiveness of drugs that are currently available for control of these diseases is limited because of cost and because drug resistance can occur. Because of their intimate contact with host components and their accessibility to host protective effector mechanisms, nematode secretory products have potential as targets vulnerable to either immune- or drug-mediated therapies. In this study we purified, characterized and cloned a unique enzyme inhibitor component of secretory products of Trichuris suis, the pig whipworm. This molecule may function as a parasite defense mechanism for evasion of host attack. These results provide the framework for development of novel control methods.

Technical Abstract: A serine protease inhibitor, termed TsCEI, was purified from adult-stage Trichuris suis by acid precipitation, affinity chromatography (elastase- agarose) and reverse phase HPLC. The molecular weight of TsCEI was estimated at 6.437 kDa by laser desorption mass spectrometry. TsCEI potently inhibited both chymotrypsin ( Ki = 33.4 pM) and pancreatic elastase ( Ki = 8.32 nM); neutrophil elastase, chymase (mouse mast cell protease-1, mMCP-1), and cathepsin G were also inhibited. Trypsin, thrombin and factor Xa were not inhibited. The cDNA-derived amino acid sequence of the mature TsCEI consisted of 58 residues including 9 cysteine residues with a molecular mass of 6.196 kDa. TsCEI displayed 48 % homology to a previously characterized trypsin/chymotrypsin inhibitor of T. suis, TsTCI. TsCEI showed limited homology (41%) to a protease inhibitor from the hemolymph of the honeybee Apis mellifera. Weak similarity was detected with the trypsin/thrombin inhibitor of the European frog Bombina bombina, the elastase isoinhibitors of Anisakis simplex, and the chymotrypsin/elastase and trypsin inhibitors of Ascaris suum. The inhibitors of T. suis, an intestinal parasite of swine, may function as components of a parasite defense mechanism by modulating intestinal mucosal mast cell-associated, protease-mediated, host immune responses.