Role of alpha-2-macroglobulin and bacterial elastase in guinea-pig pseudomonal septic shock.
An essential role of alpha-2-macroglobulin (alpha 2M) was revealed in the prevention of septic shock induced in guinea-pigs by an elastase producing strain (IFO-3455) of Pseudomonas aeruginosa. When bacterial peritonitis was induced by inoculating fibrin-thrombin clot containing viable bacteria at a dose of 10(9) c.f.u./kg body weight, the guinea-pigs (n = 6) died within 7-8 hours due to septic shock. Prior to the shock, consumption of two-thirds of the circulating alpha 2M was observed. When circulating alpha 2M was depleted 4 hours after the bacterial inoculation, the guinea-pigs immediately developed shock and died within one hour. This shock was prevented either with a specific elastase inhibitor, HONHCOCH(CH2C6H5)CO-Ala-Gly-NH2, zincov (6 microM), or with human alpha 2M. Simultaneous depletion of circulating Hageman factor also prevented shock in the alpha 2M-depleted animals. These results indicate that septic shock was induced through activation of the Hageman factor dependent system by the bacteria-produced elastase which survived alpha 2M in the circulation.
Khan
M M
MM
Department of Neuroscience and Immunology, Graduate School of Medical Sciences, Kumamoto University, Japan.
Shibuya
Y
Y
Kambara
T
T
Yamamoto
T
T
D000818:Animals; D001426:Bacterial Proteins; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood; D005174:Factor XII / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D006877:Hydroxamic Acids / Q000627:therapeutic use; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011552:Pseudomonas Infections / Q000097:blood / Q000503:physiopathology*; D011550:Pseudomonas aeruginosa; D012772:Shock, Septic / Q000097:blood / Q000503:physiopathology* / Q000517:prevention & control; D000511:alpha-Macroglobulins / Q000378:metabolism / Q000502:physiology*
D001426:Bacterial Proteins; D004731:Endotoxins; D006877:Hydroxamic Acids; D000511:alpha-Macroglobulins; C048727:zincov; D005174:Factor XII; D008666:Metalloendopeptidases; C043859:pseudolysin, Pseudomonas aeruginosa