SELECTIVE DEPLETION OF NEUTROPHILS BY A MONOCLONAL-ANTIBODY, RP-3, SUPPRESSES DEXTRAN SULFATE SODIUM-INDUCED COLITIS IN RATS

Administration of dextran sulphate sodium to animals induces acute col itis characterized by infiltration of large numbers of neutrophils int o the colonic mucosa, which histologically resembles human active ulce rative colitis. It has been reported that neutrophils and the reactive oxygen metabolites produced by them are involved in the progress of u lcerative colitis. This study was intended to clarify their roles by u sing this animal model. First, possible sources and species of reactiv e oxygen metabolites were determined using luminol-dependent chemilumi nescence with addition of enzyme inhibitors and reactive oxygen metabo lite scavengers. Next, to examine whether neutrophils and hypochlorous acid derived from them contribute to tissue injury, we administered R P-3, a monoclonal antibody capable of selectively depleting neutrophil s, and taurine, a hypochlorous acid scavenger, to rats treated with de xtran sulphate sodium. Addition of azide, taurine, catalase, superoxid e dismutase and dimethyl sulphoxide into colonic mucosal scrapings sig nificantly inhibited chemiluminescence production, but allopurinol and indomethacin had no effects. These results suggest that excessive hyp ochlorous acid, hydrogen peroxide, superoxide anion and hydroxyl radic al are generated by the inflamed colonic mucosa. Intraperitoneal injec tions of RP-3 significantly suppressed bleeding, tissue myeloperoxidas e activity, chemiluminescence production and erosion formation. On the other hand, administration of taurine tended to inhibit bleeding and erosion formation to some extent, although it could not significantly suppress them. These data suggest that neutrophils play an important r ole in the development of this colitis and that hypochlorous acid migh t be one of the causes of tissue injury induced by neutrophils.