Role of bradykinin in microbial infection: Enhancement of septicemia by microbial proteases and kinin

Data presented herein will show that bradykinin, microbial proteases which activate the kinin generating cascade, and kininase inhibitors can enhance septicemia by approximately 10 to 100 fold in mice infected intraperitoneally (i.p.) with a strain of bacteria, Pseudomonas aeruginosa 621, which does not usually produce a kinin generating protease. Bacterial spreading was evaluated either in the blood or in the spleen by colony formation on agar plates. Using the P. aeruginosa kaguma strain which produces a large amount of proteases, further experiments were carried out. Results showed that two different protease inhibitors (ovomacroglobulin and a synthetic peptide inhibitor against pseudomonal elastase) as well as a kinin antagonist suppressed bacterial dissemination to 1/10 ~1/100 of control. Similar results were observed in experiments using Vibrio vulnificus. These data support the hypothesis that microbial proteases and especially bradykinin is responsible for facilitation of microbial dissemination in vivo.