Experimental Parasitology

Rhoads, M. L., Fetterer, R. H., Hill, D. E., and Urban, J. F., Jr. 2000. Trichuris suis: A secretory chymotrypsin/elastase inhibitor with potential as an immunomodulator. Experimental Parasitology 95, 36– 44. A serine protease inhibitor, termed TsCEI, was purified from adultstage 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 5 33.4 pM) and pancreatic elastase (Ki 5 8.32 nM). Neutrophil elastase, chymase (mouse mast cell protease-1, mMCP-1), and cathepsin G were also inhibited by TsCEI, whereas trypsin, thrombin, and factor Xa were not. 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% sequence identity to a previously characterized trypsin/chymotrypsin inhibitor of T. suis, TsTCI. TsCEI showed 36% sequence identity to a protease inhibitor from the hemolymph of the honeybee Apis mellifera. Sequence similarity was also detected with the trypsin/thrombin inhibitor of the European frog Bombina bombina, the elastase isoinhibitors of the nematode Anisakis simplex, and the chymotrypsin/elastase and trypsin inhibitors of the nematode 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. Index Descriptors and Abbreviations: chymotrypsin (EC3.4.21.1) inhibitor; elastase (EC3.4.21.36) inhibitor; chymase inhibitor; cathepsin G inhibitor; nematode; in vitro cultivation; excretory/secretory products; Apis mellifera; honeybee; TsCEI, Trichuris suis chymotrypsin/ elastase inhibitor; TsTCI, T. suis trypsin/chymotrypsin inhibitor; AmCI, A. mellifera cathepsin G/chymotrypsin inhibitor; BSTI, Bombina bombina skin trypsin/thrombin inhibitor ATI, Ascaris suum trypsin inhibitor; C/E-1, A. suum chymotrypsin/elastase inhibitor; AX-SPI-1,2,3, Anisakis simplex elastase isoinhibitors; pNA, paranitroanilide; TCA,