Chemotactic peptide-induced acute colitis in rabbits.
Bacterial chemotactic peptides from the intestinal lumen could potentially induce inflammation if they reached the mucosa. We tested several peptides chemotactic for different inflammatory cells, as well as a nonchemotactic peptide, bradykinin, for their ability to induce colitis in vivo in rabbits. These peptides were also assessed for their ability to stimulate release of the eicosanoids leukotrienes B4 and C4 and prostaglandin E2 from normal rabbit colons perfused ex vivo. Intracolonic administration of n-formyl-methionyl-leucyl-phenylalanine (chemotactic for neutrophils); its methyl ester (chemotactic for monocytes), and alanyl-glycyl-seryl-glutamic acid (chemotactic for eosinophils) all produced colitis (assessed grossly and histologically) within 4 days. Bradykinin did not induce colitis although it did release prostaglandin E2. n-Formyl-methionyl-leucyl-phenylalanine methyl ester induced the greatest degree of colitis in vivo and released prostaglandin E2 and leukotrienes ex vivo. n-Formyl-methionyl-leucyl-phenylalanine and alanyl-glycyl-seryl-glutamic acid induced comparable degrees of inflammation, but alanyl-glycyl-seryl-glutamic acid produced no eicosanoid release while n-formyl-methionyl-leucyl-phenylalanine released both prostaglandin E2 and leukotriene B4 and leukotriene C4 products from normal ex vivo perfused colons. Thus alanyl-glycyl-seryl-glutamic acid produces colitis independent of proinflammatory eicosanoids while eicosanoid release could contribute to colitis produced by n-formyl-methionyl-leucyl-phenylalanine methyl ester. This experimental model of colitis may reflect one possible etiology of inflammatory bowel disease in humans, when bacterial chemotactic peptides breach mucosal defenses in susceptible individuals.
LeDuc
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Department of Medicine, Harbor-UCLA Inflammatory Bowel Disease Center, Torrance.
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D000818:Animals; D001920:Bradykinin / Q000633:toxicity; D002630:Chemotactic Factors / Q000633:toxicity*; D002631:Chemotactic Factors, Eosinophil / Q000633:toxicity*; D002634:Chemotaxis, Leukocyte; D003092:Colitis / Q000139:chemically induced*; D015232:Dinoprostone / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives / Q000633:toxicity; D009842:Oligopeptides / Q000633:toxicity*; D011817:Rabbits; D013189:SRS-A / Q000378:metabolism
D002630:Chemotactic Factors; D002631:Chemotactic Factors, Eosinophil; D009842:Oligopeptides; D013189:SRS-A; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; C063376:alanyl-glycyl-seryl-glutamic acid; C042932:formylmethionyl-leucyl-phenylalanine methyl ester; D015232:Dinoprostone; D001920:Bradykinin