Metabolism of Human Gamma Macroglobulins*

lins) are antibody containing molecules which are present normally in all animal species that have been appropriately examined. In man, the y,-macroglobulins constitute about 7 % of the total gamma globulin group and 1 to 2 % of all serum protein. They differ from the more abundant 6.6 S y-globulins in being larger (mol wt about 1,000,000), in being unable to pass the placental barrier, and in having distinctive antigenic charac-teristics (1, 2). Antibodies such as the isohemag-glutinins, typhoid 0 antibodies, and cold aggluti-nins are predominantly in the y,-macroglobulin group. Infants respond principally with macro-globulin antibodies (3-5), and in adult animals and man the response to many (perhaps all) anti-gens normally passes through an early stage in which antibody activity is entirely limited to the yi-macroglobulins (6-9). The amount of gamma macroglobulin (and macroglobulin antibody) in the serum depends on the rate and duration of macroglobulin synthe-sis and on the rate of y1-macroglobulin removal and catabolism. Previous studies in animals (9, 10) and man (11-14) have indicated that y1-macroglobulins are catabolized more rapidly than 6.6 S y-globulins. Half-times of 2 to 3 days have been reported for normal human gamma macroglobulin (11), and half-times of 6.5 to 13 days have been found with macroglobulins obtained from patients with Wal-denstroms macroglobulinemia (12, 13). In some of these studies (11), the methods used for iso-lating the 71-macroglobulin may have altered the protein and thus shortened the apparent survival. In other studies (12) where radioactive labeled amino acids were used in vivo, the apparent sur-vival may have been spuriously prolonged due to persistent radioactivity in the precursor amino * Submitted for publication October 25, 1963; accepted