Involvement of bradykinin B1 receptors in the polymorphonuclear leukocyte accumulation induced by IL-1 beta in vivo in the mouse.
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.
Ahluwalia
A
A
Department of Biochemical Pharmacology, Medical College of St. Bartholomew's Hospital, London, United Kingdom.
Perretti
M
M
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D018002:Receptors, Bradykinin / Q000187:drug effects* / Q000502:physiology*
D065168:Bradykinin Receptor Antagonists; D007375:Interleukin-1; D018002:Receptors, Bradykinin; C024626:bradykinin, des-Arg(9)-; C051090:bradykinin, Leu(8)-des-Arg(9)-; D001920:Bradykinin