Involvement of bradykinin B1 receptors in the polymorphonuclear leukocyte accumulation induced by IL-1 beta in vivo in the mouse.

Abstract

Local application of the bradykinin B1 receptor antagonist desArg9[Leu8]BK, but not the B2 receptor antagonist Hoe 140, attenuated by approximately 50% the polymorphonuclear leukocyte accumulation into 6-day-old air pouches observed in response to application of murine IL-1 beta (5 ng). The selective appearance of a chemotactic response to the bradykinin B1 receptor agonist desArg9BK only in air pouches pretreated (4 h) with IL-1 beta indicated the involvement of this receptor type during this acute inflammation model. The pro-migratory action of desArg9BK was magnified when the effect of IL-1 on polymorphonuclear leukocyte accumulation had subsided (i.e., 24 h post-IL-1). desArg9[Leu8]BK, but not Hoe 140, antagonized the effect of desArg9BK, indicating an action on B1 receptors, but not B2 receptors. The cellular infiltration observed following application of desArg9BK in IL-1-sensitized air pouches was due to the release of neuropeptides from C fibers, as indicated by the inhibitory action of the substance P antagonist, RP 67,580, and the calcitonin-gene related peptide antagonist, CGRP-(8-37). In conclusion, this study provides evidence that activation of C fibers, which is necessary for the achievement of a full chemotactic action of IL-1, is due to up-regulation (or induction) of bradykinin B1 receptors and describes, for the first time, a relationship between these receptors and polymorphonuclear leukocyte recruitment.