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1989 Fiscal Year Final Research Report Summary

ROLE OF HAGEMAN FACTOR-KALLIKREIN-KININ SYSTEM IN HOST DEFENCE AGAINST BACTERIAL INFECTIONS.

Research Project

Project/Area Number 63570167
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionKUMAMOTO UNIVERSITY

Principal Investigator

YAMAMOTO Tetsuro  Kumamoto Univ., Med. Sch., Associate Prof., 医学部, 助教授 (60112405)

Project Period (FY) 1988 – 1989
KeywordsHAGEMAN FACTOR / KALLIKREIN / KININ / VASCULAR PERMEABILITY / alpha_2MACROGLOBULIN / BACTERIAL PROTEASE / PLASMA PROTEASE / BACTERIAL INFECTION
Research Abstract

The 28,000 mw active fragment of guinea pig Hageman factor (beta-HFa), injected intradermally, induces an increased vascular permeability. To determine if prekallikrein (PK) and kallikrein(Kal) participated in the permeability induced by beta-HFa, circulating PK was depleted by intra-arterial injections of anti-PK antibody. This resulted in about 80 percent diminution in the permeability response to -HFa. Soybean trypsin inhibitor, injected simultaneously with beta-HFa, inhibited the permeability response by more than 90 percent. The soybean inhibitor blocked the activity of Kal, but did not inhibit the amidolitic capacity of beta-HFa. The permeability activity of beta-HFa was augmented 10-fold by simultaneous injection of a synthetic kinin potentiator, and was almost completely inhibited by the simultaneous injection of a kinin destroying enzyme. These results indicated that the cascade system indeed worked in vivo possessing the potential permeability enhancement capacity.
Guinea pig … More alpha_2-macroglobulin which is not only a major circulating inhibitor of tissue destructive pathogenic proteases but also of beta-HFa was immunologically depleted from three animals. Duration of the permeability reaction caused by beta-HFa was prolonged twice as long as the control, indicating a presence of negative feedback regulation of the cascade system via the circulating protease inhibitor.
Activation of the Hageman factor-kallikrein-kinin system by tissue destructive proteases derived from invasive microbe was investigated. Nine of the eleven proteases examined including a novel cysteine protease, 73k protease of Serratia marcescens, activated Hageman factor in vitro as well as in vivo resulting in the vascular permeability enhancement. Three proteases of the positive nine also activated prekallikrein directly. Remaining two proteases which activated neither HF or PK generated bradykinin-like molecule from high-molecular weight kininogen directly.
These results suggested an important role of the Hageman factor dependent permeability system in host defence especially against tissue destructive proteases derived from invasive microbe. Less

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Yamamoto,Tetsuro: "The Hageman factor dependent system in vascular permeability reaction." Biochim.Biophys.Acta. 966. 196-206 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Molla,Akhteruzzaman: "Characterization of 73kDa thiol protease from Serratia marcescens and its effect on plasma proteins." J.Biochem.104. 616-621 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto,Tetsuro: "Role of Hageman factor and related peptides as chemical mediators of inflammation." Rheumatology-SEAPAL 1988(T.Suzuta and Y.Yamauchi eds.)(Elsevier,Amsterdam). 59-60 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto,Tetsuro: "Hageman factor dependent kinin generation system in guinea pig skin." Kinins V(K.Abe,H.Moriya and S.fujii eds.)(Plenum Publishing). 447-452 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Molla,Akhteruzzaman: "Activation of Hageman factor and prekallikrein and genaration of kinin by various microbial proteinases." J.Biol.Chem.264. 10589-10594 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto, T. et al.: "The Hageman factor-dependent system in the vascular permeability reaction." Biochim. Biophs. Acta. 966. 196-206 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Molla, A. et al.: "Characterization of 73 kDa thiol protease from Serratia marcescens and its effect on plasma proteins." J. Biochem. 104, 616-621, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto, T.: "Role of Hageman factor and related peptides as chemical mediators of inflammation." Rheumatology-SEAPAL 1988 p59-60, 1989, Elsevier.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto, T. et al.: "Hageman factor dependent kinin generation system in guinea pig skin: Extravascular localization of the components, and prolonged vascular reaction in inhibitor-depleted animal of this system." Kinin V, Part A, p447-452. (1989, Plenum Publishing)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Molla, A. et al.: "Activation of Hageman factor and prekallikrein and generation of kinin by various microbial proteinases." J. Biol. Chem. 264, 10589-10594, 1989.

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-03-26  

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