Trichuris suis: a secretory chymotrypsin/elastase inhibitor with potential as an immunomodulator.
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 (K(i) = 33.4 pM) and pancreatic elastase (K(i) = 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.
Rhoads
M L
ML
Parasite Biology and Epidemiology Laboratory, Livestock and Poultry Sciences Institute, Maryland, Beltsville 20705, USA.
Fetterer
R H
RH
Hill
D E
DE
Urban
J F
JF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D017931:DNA Primers / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005260:Female; D008297:Male; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013552:Swine; D014258:Trichuris / Q000737:chemistry* / Q000276:immunology
C410971:CEI protein, Trichuris suis; D017931:DNA Primers; D004791:Enzyme Inhibitors; D011498:Protein Precursors; D011506:Proteins; D002918:Chymotrypsin; D010196:Pancreatic Elastase