Gamma Globulin Turnover and Intestinal Degradation of Gamma Globulin in the Dog.

Increased catabolism of plasma proteins by leakage into the gastrointestinal tract and subsequent digestion by the intestinal enzymes are frequently the causes of hypoproteinemia (1-5). The presence of plasma proteins has been demonstrated both in saliva and in the gastric and intestinal juice of normal individuals; therefore, gastrointestinal leakage of plasma proteins may account for a substantial part of their normal degradation (6-12). The passage of plasma al-bumin into the intestine has been studied quantitatively by 1131-labeled albumin. This technique is complicated by the secretion of inorganic iodide in saliva and gastric juice (13, 14) and by secretion and reabsorption of iodide in the small intestine (12, 15). Consequently, only transfer of protein-bound radioactivity is a measure of transfer of I131-labeled protein. In man one-third of the total amount of albumin catabolized was found to be broken down in the gastrointestinal tract (8), and in dogs from one-half to two-thirds of albumin catabolism was found to be due to gastrointestinal leakage (12). In sheep a substantial amount of albumin was recovered from the intestinal contents without inhibiting the proteolytic enzymes (9). Jeejeebhoy and Coghill (10) estimated that 50%o of albumin catabolism takes place in the gas-trointestinal tract of man; they measured fecal radioactivity after oral administration of an ion-exchange resin. Thus iodide passing into the intestinal lumen is bound by the resin and excreted in the stool. Their figure, however, may not reflect intestinal catabolism, since the fecal radioactivity may have been derived from nonprotein-bound iodide secreted in the gastrointestinal juice (15). All classes of plasma proteins seem to leak into the gastrointestinal lumen (6), but only albumin has been studied quantitatively. In the present investigation, the role of the small intestine for the catabolism of gamma globulin has been studied in the dog. The total turnover was determined by isolated and I131-labeled canine gamma globulin. Four to 7 weeks later another dose of I'31-labeled gamma globulin was injected into the same dogs, and the transfer of protein-bound radioactivity from plasma to the lumen of intestinal segments was measured. METHODS Material. The study was carried out in ten mongrel dogs weighing 4.3 to 16.5 kg. All were apparently healthy; hemoglobin, hematocrit, plasma proteins, and serum creatinine were normal. Autopsy at the end of each experiment revealed normal organs. Gamma globulin was isolated from the serum of normal dogs by column chromatography on diethylaminoethyl (DEAE) cellulose 1 (16). Serum was dialyzed …