PROPOSED ROLE FOR ALPHA-1-MACROGLOBULIN IN PROMOTION OF ALPHA-1-ACUTE-PHASE GLOBULIN SYNTHESIS BY PERFUSED RAT-LIVER

  • 1 January 1975
    • journal article
    • research article
    • Vol. 56  (6) , 570-578
Abstract
The effects of i.v. administered rat .alpha.1 macroglobulin (.alpha.1M), alone and in combination with pancreatic trypsin, on the synthesis of .alpha.1 acute-phase globulin (.alpha.1AP globulin) were measured in isolated perfused rat liver 24 h after injection. Maximum promotion (.apprx. 5-fold) of .alpha.1AP globulin synthesis was observed after administration of .alpha.1M complexed with trypsin or .alpha.1M alone, which after purification had lost most of its trypsin-protein-esterase (TPE) activity. Slightly lesser but still significant degrees of enhancement (.apprx. 4-fold) of .alpha.1AP globulin synthesis resulted from the injection of .alpha.1M alone or complexed with trypsin, which after purification had retained significant TPE activity. All these responses were greater than those generated by injection of trypsin or plasma alone, or rabbit plasma complexed with trypsin. The synthetic response did not reach the maximum rate observed 24 h after an i.m. injection of sterile turpentine. An hypothesis is proposed for the role of .alpha.1 macroglobulin (and its homolog in man, .alpha.2 macroglobulin) in the mediation of the acute-phase synthetic response by the liver. This predominantly intravascular glycoprotein serves as the principal circulatory proteinase binder. Proteinases released in response to tissue injury, necrosis or inflammation would be bound and inactivated by .alpha.1M, and in turn the .alpha.1M-proteinase complex would stimulate the liver to synthesize a number of acute-phase proteins. Some of these, e.g., .alpha.2 acute-phase globulin also possess proteinase binding activity and, being of low MW, would be more effective than .alpha.1M in the inactivation of released tissue enzymes at extravascular sites. The data are compatible with the biphasic role for plasma proteinase inhibitors in the biological response to injury.