Bradykinin augments the in vitro migration of nonsensitized lymphocytes

Bradykinin and related peptides have been considered important as mediators of acute inflammation, but their role in the cell-mediated immune response has not been extensively investigated. We have examined the effect of physiological concentrations of these autacoids on the migration of nonsensitized lymphocytes employing an in vitro micropore filter assay system. Bradykinin at a concentration of 0.01-1 nM significantly stimulated the migration of both human peripheral blood and rat splenic lymphocytes. Related naturally-occurring kinins (kallidin, MetLys-bradykinin, desArg9-bradykinin) had a similar effect but other autacoids (angiotensins I and II, histamine, serotonin) were inactive. Bradykinin was more active on freshly harvested lymphocytes than on cells incubated for up to 48 h with or without mitogen. Bradykinin appeared to act predominantly as a chemokinetic agent (augmenting random nondirectional motility), as determined by checkerboard analysis. Bradykinin appeared to exert its effect on lymphocytes predominantly through the B1 class of bradykinin receptors. The migratory response to bradykinin could not be attributed to the release of arachidonic acid metabolites, but stimulated migration could be significantly inhibited by the histamine type 2 receptor antagonist cimetidine. These studies provide a novel mechanism whereby nonsensitized lymphocytes may be recruited to sites of delayed-type hypersensitivity reactions.