Neutrophil-mediated mucosal injury. Role of reactive oxygen metabolites.
Reactive oxygen metabolites (ROMs) are partially reduced oxygen species that include superoxide, hydrogen peroxide, hydroxyl radical, and hypohalous acids. Formation of superoxide or hydrogen peroxide may be injurious to tissue directly; however, it is thought that the primary mediators of tissue damage are the secondarily derived oxidants such as hydroxyl radical and hypohalous acid. The gastrointestinal tract is particularly well endowed with the enzymatic machinery necessary to form large amounts of ROMs. Sources of ROMs in the gastrointestinal tract include mucosal oxidases such as xanthine oxidase, amine oxidase, and aldehyde oxidase as well as the NADPH oxidase found in the resident phagocytic leukocytes (macrophages, neutrophils, eosinophils) of the lamina propria. We have demonstrated that reperfusion of ischemic small intestine results in substantial mucosal injury that is mediated by oxy radicals generated from xanthine oxidase and inflammatory leukocytes. The final mediator of toxicity appears to be the hydroxyl radical derived from the iron-catalyzed interaction between superoxide and hydrogen peroxide. Data from our laboratories as well as other laboratories suggest that reactive oxygen metabolites may play an important role in mediating mucosal injury during active episodes of ulcerative colitis. We present a working hypothesis which states that transient ischemic episodes in the bowel initiate a cascade of self-perpetuating cycles of ROM formation, inflammation and, ultimately, mucosal injury.
Grisham
M B
MB
Department of Physiology and Biophysics, LSU School of Medicine, Shreveport 71130.
Granger
D N
DN
D000818:Animals; D003093:Colitis, Ulcerative / Q000209:etiology*; D003424:Crohn Disease / Q000209:etiology*; D005609:Free Radicals; D006801:Humans; D006878:Hydroxides; D017665:Hydroxyl Radical; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply; D007511:Ischemia; D009504:Neutrophils / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*
D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D010100:Oxygen