Neutrophil-independence of the initiation of colonic injury. Comparison of results from three models of experimental colitis in the rat.
Although the role of neutrophils in the pathogenesis of several forms of gastrointestinal injury has been well demonstrated, their role in the development of experimental colonic injury is less clear. To examine whether neutrophils play a role in the development of experimental colitides, the effects of a sustained neutropenia on multiple indices of colonic injury in rats was examined 24 hr following the initiation of colitis with the intrarectal application of acetic acid, trinitrobenzene sulfonic acid (TNBS)-ethanol, or the potent proinflammatory agent, phorbol-12-myristate-13-acetate (PMA). In comparison to animals with normal neutrophil counts and colitis induced by any of the three agents, no attenuation in macroscopic damage or histopathologic injury was observed in neutropenic animals exhibiting a greater than 95% reduction in circulating neutrophils and 85% reduction in tissue-associated myeloperoxidase activity. Although the tissue edema associated with acetic acid or PMA-induced colitis was not reduced by neutropenia, the colonic edema associated with TNBS colitis was attenuated by prior neutrophil depletion with anti-neutrophil antiserum. Despite our initial hypothesis that neutrophils played a key role in the genesis of experimental colitis (especially that induced by PMA), the results demonstrated that these cells are not essential for the development of the major pathological features of colitis induced by this agent, acetic acid, or TNBS. Although these results support the proposal that in these models of colitis, inflammation develops secondary to injury (rather than the converse), further studies will be necessary to elucidate the role of inflammatory cells other than neutrophils in the genesis of experimental colitides.
Buell
M G
MG
Department of Medicine, Queen's University, Kingston, Ontario, Canada.
Berin
M C
MC
D000085:Acetates; D019342:Acetic Acid; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D003106:Colon / Q000473:pathology*; D000431:Ethanol; D007958:Leukocyte Count; D008297:Male; D009503:Neutropenia / Q000473:pathology; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid
D000085:Acetates; D000431:Ethanol; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate; D019342:Acetic Acid