Involvement of
bradykinin generation in bacterial invasion was examined by using a gram-negative bacillus, Vibrio vulnificus, which is known to invade the blood circulatory system and cause
septicemia. V. vulnificus was injected intraperitoneally (i.p.) into mice with or without
bradykinin or a
bradykinin (B2 receptor) antagonist. Dissemination of V. vulnificus from peritoneal septic foci to the circulating blood was assessed by counting of viable bacteria in venous blood by use of the colony-forming assay. Intravascular dissemination of V. vulnificus in mice was significantly potentiated by simultaneous injection with
bradykinin but was markedly reduced by coadministration with the B2 antagonist D-Arg,[Hyp3, Thi(5,8), D-Phe7]-
bradykinin. Furthermore, V. vulnificus lethality was significantly increased when
bradykinin was administered simultaneously with the bacillus, whereas it was definitely suppressed by treatment with D-Arg,[Hyp3, Thi(5,8), D-Phe7]-
bradykinin. Similarly,
ovomacroglobulin, a potent inhibitor of the V. vulnificus
protease, showed a strong suppressive effect on the V. vulnificus
septicemia. We also confirmed appreciable
bradykinin production in the primary septic foci in the mouse peritoneal cavity after i.p. inoculation with V. vulnificus. It is thus concluded that
bradykinin generation in infectious foci is critically involved in facilitation of intravascular dissemination of V. vulnificus.