Alpha-2-macroglobulin as the major defence in acute pseudomonal septic shock in the guinea-pig model.

Abstract

An intravenous injection of 1.2 mg/kg of Pseudomonas aeruginosa elastase induces immediate lethal shock in guinea-pigs. In the present study, alpha-2-macroglobulin (alpha 2M) was shown to be the major factor in guinea-pig plasma that inhibits the enzymatic activity of elastase in vitro. Depletion of circulating alpha 2M by injecting anti-guinea-pig alpha 2M rabbit IgG F(ab')2 rendered the animals sensitive to a dose of elastase of 0.05 mg/kg. When the alpha 2M-depleted guinea-pigs were reconstituted with human alpha 2M, this sensitivity was reversed. Lethal shock did not occur in alpha 2M-depleted animals even at an elastase dose of 0.2 mg/kg when Hageman factor was simultaneously depleted, indicating that elastase induces shock through activation of the Hageman factor-dependent system. Similar results were obtained when the culture supernatants of an elastase-producing strain, IFO-3455, were used instead of the purified elastase, whereas no cardiovascular changes occurred, even in the alpha 2M-depleted guinea-pigs, when the culture supernatants were pretreated with an elastase specific inhibitor (zincov) or when the culture supernatants of an elastase non-producing strain, PA-103 were used.

• Authors: M M Khan, Y Shibuya, T Nakagaki, T Kambara, T Yamamoto
• Journal: International journal of experimental pathology (Int J Exp Pathol) Vol. 75 Issue 4 Pg. 285-93 (Aug 1994) ISSN: 0959-9673 [Print] England
• PMID: 7524612 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• alpha-Macroglobulins
• Factor XII
• Pancreatic Elastase

Topics

• Acute Disease
• Animals
• Cell-Free System
• Disease Models, Animal
• Factor XII (metabolism)
• Female
• Guinea Pigs
• Male
• Pancreatic Elastase (antagonists & inhibitors)
• Pseudomonas Infections (blood)
• Shock, Septic (blood, chemically induced)
• alpha-Macroglobulins (metabolism, pharmacology, physiology)