Role of alpha-2-macroglobulin and bacterial elastase in guinea-pig pseudomonal septic shock.

Abstract

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.

• Authors: M M Khan, Y Shibuya, T Kambara, T Yamamoto
• Journal: International journal of experimental pathology (Int J Exp Pathol) Vol. 76 Issue 1 Pg. 21-8 (Feb 1995) ISSN: 0959-9673 [Print] England
• PMID: 7537522 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• Endotoxins
• Hydroxamic Acids
• alpha-Macroglobulins
• zincov
• Factor XII
• Metalloendopeptidases
• pseudolysin, Pseudomonas aeruginosa

Topics

• Animals
• Bacterial Proteins
• Disease Models, Animal
• Endotoxins (blood)
• Factor XII (physiology)
• Female
• Guinea Pigs
• Hydroxamic Acids (therapeutic use)
• Male
• Metalloendopeptidases (antagonists & inhibitors, physiology)
• Pseudomonas Infections (blood, physiopathology)
• Pseudomonas aeruginosa
• Shock, Septic (blood, physiopathology, prevention & control)
• alpha-Macroglobulins (metabolism, physiology)