PRETREATMENT WITH ALPHA(2)-MACROGLOBULIN LEADS TO RECOVERY OF RATS EXPOSED TO A LETHAL SCALD

The effect of alpha2-macroglobulin (alpha2M) administration on the sur vival rate of lethally injured rats and molecular mechanisms regulatin g its hepatic expression after sublethal and lethal scalding were exam ined. Transcriptional activity of nuclei for the alpha2M gene increase d after a sublethal 20 per cent TBSA scald reaching a maximal three-fo ld 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 alpha2M le vel increased during the first few hours, then dropped rapidly below t he control value although the abundance of its mRNA was several fold e nhanced. This anomaly was ascribed to inhibition of the alpha2M mRNA t ranslation caused by the second scald-induced disturbance of the haemo dynamic equilibria. Eighty per cent of rats receiving alpha2M prior to rescalding survived the second injury. Their recovery proceeded in pa rallel with normalization of the plasma volume and reactivation of the process of acute phase protein synthesis in the liver. A functional l ink between these events is discussed.