Pretreatment with alpha 2-macroglobulin leads to recovery of rats exposed to a lethal scald

The effect of alpha 2-macroglobulin (alpha 2M) administration on the survival rate of lethally injured rats and molecular mechanisms regulating its hepatic expression after sublethal and lethal scalding were examined. Transcriptional activity of nuclei for the alpha 2M gene increased after a sublethal 20 per cent TBSA scald reaching a maximal three-fold increase by 12 h, whereas concentrations of the corresponding mRNA and protein attained the maximal nine- and 18-fold enhancements by 24 h, respectively. After the second, lethal scald, the plasma alpha 2M level increased during the first few hours, then dropped rapidly below the control value although the abundance of its mRNA was several fold enhanced. This anomaly was ascribed to inhibition of the alpha 2M mRNA translation caused by the second scald-induced disturbance of the haemodynamic equilibria. Eighty per cent of rats receiving alpha 2M prior to rescalding survived the second injury. Their recovery proceeded in parallel with normalization of the plasma volume and reactivation of the process of acute phase protein synthesis in the liver. A functional link between these events is discussed.