HAMSTER ALPHA-MACROGLOBULIN AND MURINOGLOBULIN - COMPARISON OF CHEMICAL AND BIOLOGICAL PROPERTIES WITH HOMOLOGS FROM OTHER MAMMALS

Alpha-Macroglobulin and murinoglobulin were purified to homogeneity fr om Syrian hamster plasma and their properties were compared with those of their respective homologs from other mammals. The trypsin-inhibiti ng capacity of hamster murinoglobulin was much weaker than those of ra t and mouse murinoglobulins. Hamster alpha-macroglobulin was cleaved b y trypsin at a number of sites whereas the human homolog was split ess entially only in a ''bait'' region into two fragments of similar size. Hamster alpha-macroglobulin treated with methylamine differed from th at treated with trypsin in the electrophoretic mobility, intensity of fluorescence induced by binding of bis(8-anilino-1-naphthalenesulfonat e), and plasma clearance pattern, whereas virtually no difference was observed between the human homologs treated in the same manner. The re action of hamster alpha-macroglobulin with methylamine, as measured by the generation of thiol groups and the decrease in trypsin-protein am idase activity, was much slower than that of the human homolog. Trypsi n in a complex with hamster alpha-macroglobulin retained its fibrinoly tic activity, but this was not the case for human or rabbit alpha-2-ma croglobulin. These results suggest that, compared with the human homol og, hamster alpha-macroglobulin is more loosely packed in the native s tate, undergoes conformational change more slowly on treatment with me thylamine, and less efficiently hinders the access of proteinaceous su bstrates to trapped proteinase. The serum concentration of hamster alp ha-macroglobulin was 6.9 mg/ml, or about 3-fold higher than that of th e human type, and showed little change during the acute-phase reaction . These results account for the fact that pulmonary emphysema can be r eadily produced in hamsters by intratracheal inhalation of elastase or papain: the inhaled proteinase may be trapped by alpha-macroglobulin in much greater amounts than by other proteinase inhibitors since the alpha-macroglobulin concentration is high, and the trapped proteinase may be more potent for destroying the extracellular matrix than that t rapped by alpha-macroglobulins from other species, since hamster alpha -macroglobulin is much less efficient in hindering the access of prote inaceous substrates. These events may eventually lead to the developme nt of emphysema.