Enzymes degrading bacterial chemotactic F-met peptides in human ileal and colonic mucosa.
Bacterial chemotactic F-met peptides have been identified in culture supernatants of intestinal bacteria and in human faecal dialysates. These potent inflammatory agents could play a role in intestinal inflammatory disorders should they cross the epithelial barrier of the gut. We have identified mucosal peptidases which degrade F-met-leu-phe (FMLP) in ileal and colonic mucosal biopsies obtained at colonoscopy. A carboxypeptidase, inhibited by D-L-benzyl succinate (BzS), accounted for more than 60% of total FMLP-ase activity, other uncharacterized peptidases contributing the rest of the activity against the intact peptide. An F-met deformylase, inactive against di- and tri-peptides, cleaves released F-met completing the degradation. Total FMLP-ase, carboxypeptidase and F-met deformylase activities were measured in serial mucosal biopsies from 15 control patients undergoing colonoscopy for occult bleeding with negative findings and from 15 patients with ulcerative colitis (UC) and 10 with Crohn's disease (CD). Highest activities were found in terminal ileum and lowest in the rectum. Total FMLP-ase and carboxypeptidase activities were similar in controls and UC patients but were substantially reduced in CD, especially in the terminal ileum (controls 493 +/- 146 and 116 +/- 73 nmol/100 micrograms protein per h, respectively and CD 231 +/- 96 and 41 +/- 36 nmol/100 micrograms protein per h, respectively (P = 0.0018 and 0.015). F-met deformylase activities were similar in all groups. There was no correlation between enzyme activity and severity of inflammation. FMLP degrading peptidases probably contribute to the mucosal barrier of the gut in regions of high bacterial colonization, limiting intestinal absorption and inflammatory responses to these potent bacterial products in the intestinal lumen.
Chadwick
V S
VS
Wellcome Medical Research Institute, University of Otago Medical School, Dunedin, New Zealand.
Schlup
M M
MM
Cooper
B T
BT
Broom
M F
MF
D000581:Amidohydrolases / Q000302:isolation & purification / Q000378:metabolism; D002268:Carboxypeptidases / Q000302:isolation & purification / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000201:enzymology; D003106:Colon / Q000201:enzymology*; D003424:Crohn Disease / Q000201:enzymology; D010450:Endopeptidases / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000201:enzymology*; D007413:Intestinal Mucosa / Q000201:enzymology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism*
D009240:N-Formylmethionine Leucyl-Phenylalanine; D002268:Carboxypeptidases; D010450:Endopeptidases; D000581:Amidohydrolases; C020150:formylmethionine deformylase