The Acute-Phase Protein Alpha(2)-Macroglobulin Plays An Important Role in Radioprotection in the Rat

Abstract

The importance of alpha(2)-macroglobulin (alpha(2)M) in natural radioprotection was studied by examining its radioprotective effectiveness in rat models of exogenously and endogenously, preexposure-increased alpha(2)M. Radioprotective efficacy was ascertained by the postirradiation survival rate, the restoration of body weight, and the leukocyte count, which were monitored during a 4-week follow-up period. The results were compared with the effects of a pretreatment with the synthetic radioprotective agent amifostine (Ami), which provides 100% protection in rats whole-body-irradiated by x-rays given in a dose of 6.7 Gy (LD(50/30)). Raising the plasma concentration of alpha(2)M 15-fold in male rats by a single intraperitoneal injection of purified protein provided 100% survival of irradiated animals. Female rats on the 19th day of pregnancy with endogenously elevated levels of alpha(2)M displayed improved survival (80%) compared with untreated rats (50% survival). After alpha(2)M administration, the pregnant, irradiated rats exhibited 100% survival. In both males and pregnant females, alpha(2)M administration promoted body weight and leukocyte postirradiation recovery as in Ami-pretreated rats. These findings, together with our observation that Ami administration induced a 45-fold increase in alpha(2)M in the circulation, led us to conclude that alpha(2)M has an essential role in both natural and amifostine-mediated radioprotection in the rat.