title: Alpha-macroglobulin-like plasma inactivator for Vibrio vulnificus metalloprotease.
abstract: The metalloprotease produced by Vibrio vulnificus (VVP) is known to be quickly inactivated by plasma proteins which belong to the class of alpha-macroglobulins in vitro at a molar ratio of 1:1. But the in vivo potential of the inactivators has not been studied. Macroalbumin (MA), a member of alpha-macroglobulins in guinea pig plasma, was found to inactivate VVP by means of physical entrapment in vitro. In vivo actions of VVP, permeability-enhancing and hemorrhagic actions, were greatly augmented by simultaneous injection of the antibody against MA, which had no effect on in vitro proteolytic action toward azocasein. The interstitial-tissue space in the normal guinea pig skin contains a negligible amount of MA. However, sufficient MA was present in the extravascular fluid collected after the intradermal injection of VVP. Besides, in the extravascular fluid, VVP formed a complex with MA and no inactivator other than MA was found. These results indicate that plasma MA leaked from the vascular system owing to the permeability-enhancing and hemorrhagic actions of VVP, resulting in inactivation of VVP in situ.
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University.
authors.forename: S
authors.initials: S
authors.lastname: Miyoshi
authors.forename: S
authors.initials: S
authors.lastname: Shinoda
mesh_terms: D000818:Animals; D000906:Antibodies; D002850:Chromatography, Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007610:Kallikreins / Q000097:blood / Q000378:metabolism; D007700:Kinetics; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014733:Vibrio / Q000201:enzymology*; D000511:alpha-Macroglobulins / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D000511:alpha-Macroglobulins; D007610:Kallikreins; D008666:Metalloendopeptidases