title: A proposed role for alpha1 macroglobulin in the promotion of alpha1 acute-phase globulin synthesis by the perfused rat liver.
abstract: The effects of intravenously administered rat alpha1 macroglobulin (alpha1M), alone and in combination with pancreatic trypsin, on the synthesis of alpha1 acute-phase globulin (alpha1AP globulin) have been measured in the isolated perfused rat liver 24 h after injection. Maximum promotion (approximately five-fold) of alph1AP globulin synthesis was observed after administration of alpha1M complexed with trypsin or alpha1M alone, which after purification had lost most of its trypsin-protein-esterase (T.P.E.) activity. Slightly lesser but still significant degrees of enhancement (approximately four-fold) of alpha1AP globulin synthesis resulted from the injection of alpha1M alone or complexed with trypsin, which after purification had retained sitnificant T.P.E. activity. All these responses were greater than those generated by injection of trypsin or plasma alone, or rabbit plasma complexed with trypsin. However, the synthetic response did not reach the maximum rate observed 24 h after an intramuscular injection or sterile turpentine. An hypothesis is proposed for the role of alpha1 macroglobulin (and its homologue in man, alpha2 macroglobulin) in the mediation of the acute-phase synthetic response by the liver. This predominantly intravascular glycoprotein serves as the principal circulatory porteinase binder. Proteinases released in response to tissue injury, necrosis or inflammation would be bound and inactivated by alpha1M, and in turn the alpha1M-proteinase complex would stimulate the liver to synthesize a number of acute-phase proteins. Certain of these, e.g. alpha2 acute-phase globulin also possess proteinase binding activity and, being of low molecular weight, would be more effective than alpha1M in the inactivation of released tissue enzymes at extravascualr sites. The data presented in this paper are compatible with this biphasic role for plasma proteinase inhibitors in the biological response to injury.
mesh_terms: D000418:Albumins / Q000096:biosynthesis; D000818:Animals; D004338:Drug Combinations; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D014357:Trypsin / Q000378:metabolism / Q000494:pharmacology*; D000511:alpha-Macroglobulins / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000418:Albumins; D004338:Drug Combinations; D000511:alpha-Macroglobulins; D014357:Trypsin