Role of Hageman factor/kallikrein-kinin system in pseudomonal elastase-induced shock model.
The role of the Hageman factor dependent pathway in pseudomonal elastase-induced shock was investigated in guinea pigs. Presence of a bradykinin B2 receptor antagonist [D-Arg0,Hyp3,Thi5,8,D-Phe7]-bradykinin (200 nM) in the circulation prevented shock caused by an intrajugular injection of pseudomonal elastase (0.8 mg/kg body weight). During the lethal shock caused by elastase (1.2 mg/kg), a significant consumption of components of the Hageman factor/kallikrein-kinin system was observed such as 45.7 +/- 2.20% consumption of Hageman factor, 100 +/- 0% of prekallikrein, and 85.1 +/- 2.50 of high-molecular-weight kininogen. More striking evidence for the participation of this system was demonstrated in depletion experiments with monospecific F(ab')2 antibodies against the components of the system. After depletion of any one of the components, guinea pigs exhibited unresponsiveness to the same lethal dose of pseudomonal elastase in regard to the cardio-respiratory alterations. In vitro, pseudomonal elastase (60 micrograms/ml) possessed a capacity to generate substantial amount of bradykinin in undiluted plasmas of humans (300.0 +/- 32.16 ng/ml) as well as guinea pigs (460.2 +/- 20.67 ng/ml) at 37 degrees C but not in those deficient in Hageman factor or prekallikrein. These results strongly suggested a pathological role of elastase in pseudomonal sepsis through activation of the Hageman factor dependent pathway.
Division of Molecular Pathology, Graduate School of Medical Sciences, Kumamoto, Japan.
M M
MM
Khan
T
T
Yamamoto
H
H
Araki
Y
Y
Shibuya
T
T
Kambara
D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure; D001920:Bradykinin / Q000096:biosynthesis; D004195:Disease Models, Animal; D005174:Factor XII / Q000032:analysis / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D016234:Kallikrein-Kinin System / Q000187:drug effects / Q000502:physiology*; D007704:Kininogens / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000633:toxicity*; D011288:Prekallikrein / Q000032:analysis; D011550:Pseudomonas aeruginosa / Q000201:enzymology; D012772:Shock, Septic / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control
D007704:Kininogens; D005174:Factor XII; D011288:Prekallikrein; D010196:Pancreatic Elastase; D001920:Bradykinin