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 (CINCs) in neutrophil infiltration of ulcerated gastric tissue in rats. Neutrophil chemotactic and myeloperoxidase (MPO) activities were negligible in the normal mucosa but were markedly elevated by ulceration. The activities decreased with spontaneous ulcer healing, but remained quite high when the healing was prevented by indomethacin. Neither CINC-1 nor CINC-2alpha was detected, and CINC-3 was negligible in the normal mucosa. The expression of these CINCs was also promoted by ulceration, but the expression patterns during ulcer healing were apparently different among them. The change in net content of CINCs was well associated with those in chemotactic and MPO activities during spontaneous healing. The chemotactic activity due to the net CINCs was equivalent to most parts of the activity extracted from the tissue. On the other hand, indomethacin did not affect CINC expression, compared with that in spontaneous healing, but induced the expression of high-molecular-weight (>40-kDa) chemoattractant when ulcer healing was impaired. The chemotactic activity due to >40-kDa chemoattractant was equivalent to the activity extracted from the tissue. We conclude that CINCs play crucial roles in neutrophil infiltration of ulcerated gastric tissue in the spontaneous healing in rats and that the expression of CINCs might be differentially regulated. Furthermore, the >40-kDa chemoattractant might be the predominant contributor to the increased neutrophil infiltration in the delayed healing by indomethacin.