• Open Access

Involvement of the Kinin-generating Cascade in Enhanced Vascular Permeability in Tumor Tissue

Authors

  • Yasuhiro Matsumura,

    1. Department of Microbiology, Institute for Medical Immunology, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860
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  • Masami Kimura,

    1. Department of Microbiology, Institute for Medical Immunology, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860
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  • Tetsuro Yamamoto,

    1. Department of Allergy, Institute for Medical Immunology, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860
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  • Hiroshi Maeda

    Corresponding author
    1. Department of Microbiology, Institute for Medical Immunology, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860
    • To whom correspondence should be sent.

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Abstract

Enhanced vascular permeability in tumor tissue has profound pathological consequences in tumor biology. However, details of the mechanism involved are not clear. The present work on tumor vascular permeability has led to the following three findings, (i) Ascitic tumor fluid contained kinin (about 1-40 ng/ml), which is known to enhance vascular permeability and induce pain in vivo, (ii) Kinin is generated via the kallikrein-dependent cascade in the ascitic tumor fluid. By blocking this kinin-generating cascade with Kunitz-type soybean trypsin inhibitor the formation of ascites was suppressed, (iii) Blocking of kinin-degrading enzymes (kininases I and II) by an appropriate kininase inhibitor (e.g., captopril) may result in increased permeability, leading to accumulation of the ascitic fluid. This phenomenon was verified by an about 1.2-1.5 fold increase in leakage of 51Cr-labeled bovine serum albumin into the ascites when kininase inhibitors had been administered orally 30 min before intravenous administration of the bovine serum albumin.

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