Differential sensitivity of macrophages to bradykinin.

Abstract

In this report, we investigated the responsiveness of subpopulations of elicited peritoneal macrophages between each other compared to resident tissue macrophages of alveoli of guinea pig to the action of bradykinin. Bradykinin stimulated the secretion of superoxide radical, arachidonic acid and prostaglandin E2 (PGE2) via the bradykinin B2 receptor subtype in peritoneal macrophages, indicated by complete inhibitory effect of the bradykinin B2 receptor antagonist HOE 140. The extent of the secretion, however, varied substantially between macrophages of different size. The highest level of the secretion was observed in the fraction containing the intermediate-size macrophages, while progressively lower level of the secretion was observed with decreasing size. In contrast, large macrophages obviously lost their secretory ability. Additionally, the bradykinin-stimulated release of cyclooxygenase products exerted an inhibitory action on NADPH-oxidase activity depending on size and stage of maturation/activation of macrophages, as judged by an increase in superoxide radical generation by indomethacin (100 microM) preincubation of cells. Furthermore, the investigation of resident tissue macrophages of alveoli has shown that these cells also express the bradykinin B2 receptor subtype. However, the receptor activity measured by bradykinin-induced increase in intracellular free calcium [Ca2+]i was very low compared to elicited peritoneal macrophages. These findings indicate that the stage of differentiation/maturation and activation of macrophages may be important for the ability of bradykinin to stimulate these cells to inflammatory responses in vivo.