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-induced neutrophil chemoattractants (CINC s) in neutrophil infiltration of ulcerated gastric tissue in rats. Neutroph il chemotactic and myeloperoxidase (MPO) activities were negligible in the normal mucosa but were markedly elevated by ulceration. The activities decr eased with spontaneous ulcer healing, but remained quite high when the heal ing was prevented by indomethacin. Neither CINC-1 nor CINC-2 alpha was dete cted, and CINC-3 was negligible in the normal mucosa. The expression of the se CINCs was also promoted by ulceration, but the expression patterns durin g ulcer healing were apparently different among them. The change in net con tent of CINCs was well associated with those in chemotactic and MPO activit ies during spontaneous healing. The chemotactic activity due to the net CIN Cs was equivalent to most parts of the activity extracted from the tissue. On the other hand, indomethacin did not affect CINC expression, compared wi th that in spontaneous healing, but induced the expression of high-molecula r-weight (>40-kDa) chemoattractant when ulcer healing was impaired. The che motactic activity due to >40-kDa chemoattractant was equivalent to the acti vity extracted from the tissue. We conclude that CINCs play crucial roles i n neutrophil infiltration of ulcerated gastric tissue in the spontaneous he aling in rats and that the expression of CINCs might be differentially regu lated. Furthermore, the >40-kDa chemoattractant might be the predominant co ntributor to the increased neutrophil infiltration in the delayed healing b y indomethacin.