Evidence for Species' Differences in the Effect of Serum Γ-globulin Concentration on Γ-globulin Catabolism

The fractional rates of catabolism of isotopically labeled mouse, human, bovine, and guinea pig gamma-globulins and human serum albumin were determined in mice and in guinea pigs whose serum gamma-globulin and serum albumin levels were elevated by immunization or by injections of exogenous serum proteins. These serum proteins were also followed in mice with different serum gamma-globulin levels due to different bacterial environments. The fractional rates of catabolism of the labeled gamma-globulins from all species tested were markedly increased in mice with elevated gamma-globulins due to immunization; to injections of human, mouse, guinea pig, or rabbit gamma-globulins; to exposure to supra normal numbers of bacteria in the environment. Injections of bovine gamma-globulin were only partially effective, and injections of human serum albumin had no effect. The gamma-globulin catabolic rates were decreased in mice with subnormal serum gamma-globulin levels (germfree mice). The catabolic rate of human serum albumin was essentially the same in all mice in spite of differences in serum gamma-globulin levels. In contrast, elevation of the serum gamma-globulin levels by injections of exogenous gamma-globulins or by hyperimmunization with keyhole limpet hemocyanin produced no change in the fractional catabolic rates of the isotopically labeled gamma-globulins and labeled albumin in guinea pigs. Thus, a feedback mechanism for the control of the serum gamma-globulin concentration appears to be operative in the mouse, but not in the guinea pig. Guinea pigs immunized with antigens in complete Freund's adjuvant or a saline suspension of killed E. coli had an increase in the catabolic rates of all labeled proteins tested including human serum albumin. Evidence is presented that the mechanism of this increase in catabolism is not the same as that seen in mice with elevated serum gamma-globulin levels.