Relationship between arachidonic acid metabolism, myeloperoxidase activity and leukocyte infiltration in a rat model of inflammatory bowel disease.
The relationship between 14C-arachidonic acid (14C-AA) metabolism, myeloperoxidase activity (MPO) and leukocyte infiltration was studied in a chronic model of inflammatory bowel disease, induced by a single intrarectal application of the hapten, trinitrobenzene sulphonic acid (TNB). The colonic damage produced by TNB was accompanied, after 12-36 hours, by a marked increase in MPO, which was directly correlated to leukocyte infiltration, assessed histologically. There was also a marked increase in the metabolism of 14C-AA, by homogenates of inflamed colon, to 12-, 15-HETE and 6-keto-PGF1 alpha as indices of lipoxygenase and cyclo-oxygenase metabolism respectively. However, a further increase in MPO-cellular infiltration, between 36-72 hours after TNB, was accompanied by a reduction in 12- and 15-HETE formation. The increase in MPO-cellular infiltration was maintained for up to 3 weeks, at which time both 12-, 15-HETE and 6-keto-PGF1 alpha formation had returned to control levels. These results suggest that these AA metabolites have a greater importance in the acute phase of the inflammatory response induced by TNB compared to the later chronic phase.
Boughton-Smith
N K
NK
Department of Mediator Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, U.K.
Wallace
J L
JL
Whittle
B J
BJ
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014302:Trinitrobenzenesulfonic Acid
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase