Kallikrein-kinin in infection and cancer

Hiroshi Maeda, Jun Wu, Tatsuya Okamoto, Keishi Maruo, Takaaki Akaike

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)


This review article describes the mechanism of enhancement of vascular permeability in infectious disease and cancer. This phenomenon is primarily mediated by bradykinin, nitric oxide and other unique vascular mediators. They are highly intermingled with each other in these disease states. Furthermore, these mediators are elicited in various in vivo settings most frequently induced by bacterial proteases, and indirect or direct activation of kallikrein-kinin cascade at one or more steps. The key steps involve bacterial proteases or cellular components including lipopolysaccharides. Thus, the use of appropriate protease inhibitors or antagonists, or scavengers in the case of nitric oxide, superoxide or peroxynitrite, are anticipated to attenuate the clinical manifestation induced by such mediators. It also explained that fluid accumulation in ascitic or pleural compartments in the case of carcinomatosis in terminal cancer patients can be largely attributed to bradykinin or related mechanism. Systemic bacterial dissemination is also facilitated by bradykinin, or suppressed by kinin antagonists as well as by the inhibition of kinin production, respectively. Thus, control of the level of such vascular mediators appears important both in infectious disease and in cancer. α1-Protease inhibitor, which inhibits neutrophil elastase, is inactivated by oxidative metabolites such as superoxide and peroxynitrite, and this effect activates matrix metalloproteinases. This indicates that oxidative stress activates proteolytic potential, and thus accelerates the degenerative process upon infection. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)115-128
Number of pages14
Issue number2-3
Publication statusPublished - 1999 Sept


  • α-Protease inhibitor
  • HOE 140
  • Kinin cascade
  • Matrix metalloproteinases
  • Nitric oxide
  • Peroxynitrite
  • Vascular permeability


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