Involvement of the kidney in catabolism of human leukocyte interferon.
The metabolic fate of human leukocyte interferon (HuIFN-alpha) was studied after intravenous injection into rats and cynomolgus monkeys. At various intervals the animals were sacrificed and the HuIFN-alpha content determined in serum and various tissues. HuIFN-alpha quickly disappeared from the circulation and was found mainly in the kidneys, in which levels were at least 7- to 10-fold higher than in the liver, spleen, lungs, heart, brain and muscles. No interferon was detected in urine. Subcellular fractionation of kidney revealed that the mitochondrial-lysosomal fraction (15 000 g) had a high HuIFN-alpha content. It was also found that HuIFN-alpha was rapidly inactivated by two types of proteinases found in the lysosomal fractions of rat, monkey and human kidneys, with an optimal pH of 3 to 4. The inactivation was partially inhibited by either pepstatin or leupeptin. Inactivation was totally prevented by a mixture of both inhibitors. Since it is known that interferon is scantily excreted in urine, our findings suggest that the kidney serves as a main site for its degradation.
D000818:Animals; D006801:Humans; D007372:Interferons / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D007976:Leupeptins / Q000494:pharmacology; D008247:Lysosomes / Q000378:metabolism; D008252:Macaca fascicularis; D008928:Mitochondria / Q000378:metabolism; D010436:Pepstatins / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution
D007976:Leupeptins; D010436:Pepstatins; D007372:Interferons; D010447:Peptide Hydrolases