Cytokine-induced neutrophil chemoattractants in healing of gastric ulcers in rats: expression of >40-kDa chemoattractant in delayed ulcer healing by indomethacin.

We examined the roles of cytokine-inducedneutrophil chemoattractants (CINCs) in neutrophilinfiltration of ulcerated gastric tissue in rats.Neutrophil chemotactic and myeloperoxidase (MPO)activities were negligible in the normal mucosa but weremarkedly elevated by ulceration. The activitiesdecreased with spontaneous ulcer healing, but remainedquite high when the healing was prevented byindomethacin. Neither CINC-1 nor CINC-2α was detected,and CINC-3 was negligible in the normal mucosa. Theexpression of these CINCs was also promoted byulceration, but the expression patterns during ulcerhealing were apparently different among them. Thechange in net content of CINCs was well associated withthose in chemotactic and MPO activities duringspontaneous healing. The chemotactic activity due to the net CINCs was equivalent to most parts of theactivity extracted from the tissue. On the other hand,indomethacin did not affect CINC expression, comparedwith that in spontaneous healing, but induced the expression of high-molecular-weight(>40-kDa) chemoattractant when ulcer healing wasimpaired. The chemotactic activity due to >40-kDachemoattractant was equivalent to the activity extractedfrom the tissue. We conclude that CINCs play crucialroles in neutrophil infiltration of ulcerated gastrictissue in the spontaneous healing in rats and that theexpression of CINCs might be differentially regulated. Furthermore, the >40-kDa chemoattractantmight be the predominant contributor to the increasedneutrophil infiltration in the delayed healing byindomethacin.