TY - JOUR
T1 - The Kidney is the Main Site of Interferon Degradation
AU - Bino, Tamar
AU - Madar, Zacharia
AU - Gertler, Arieh
AU - Rosenberg, Hagai
PY - 1982
Y1 - 1982
N2 - Male Sprague Dawley rats (300 g) were infused by constant infusion into the jugular vein through 3–5 h with human leukocyte-derived interferon (HuIFN-α 106 units/h, 0.9 ml/h). Blood samples were collected every 20 min through the carotid. A steady-state level of interferon in serum (104 U/ml) was reached after 50 min of infusion, indicating fast removal of most of the infused material. Examination of interferon distribution in various tissues at the termination of the infusion revealed that over 85% of active interferon was found in the kidneys. No interferon was found in urine. Ligation of both kidneys resulted (after 2.5 h of infusion) in a ten-fold increase in interferon in serum and a minor increase in other tissues. No interferon was found in the kidneys. Simultaneous infusion of HuIFN-α, pepstatin and leupeptin (the well-known inhibitors of lysosomal proteinases) for 2.5 h had no effect on interferon concentration in serum and various tissues except in kidneys where a 5-fold increase was found. Mitochondrial-lysosomal fractions contained 55% of the total kidney interferon. Partial inhibition of proteolytic and HuIFN-α degrading activities at that fraction was also observed. These data, together with our previous findings of accumulation of injected interferon in the mitochondrial-lysosomal fraction of rats and monkeys' kidney cells, provide a further evidence for the main role of the kidney in HuIFN-α degradation.
AB - Male Sprague Dawley rats (300 g) were infused by constant infusion into the jugular vein through 3–5 h with human leukocyte-derived interferon (HuIFN-α 106 units/h, 0.9 ml/h). Blood samples were collected every 20 min through the carotid. A steady-state level of interferon in serum (104 U/ml) was reached after 50 min of infusion, indicating fast removal of most of the infused material. Examination of interferon distribution in various tissues at the termination of the infusion revealed that over 85% of active interferon was found in the kidneys. No interferon was found in urine. Ligation of both kidneys resulted (after 2.5 h of infusion) in a ten-fold increase in interferon in serum and a minor increase in other tissues. No interferon was found in the kidneys. Simultaneous infusion of HuIFN-α, pepstatin and leupeptin (the well-known inhibitors of lysosomal proteinases) for 2.5 h had no effect on interferon concentration in serum and various tissues except in kidneys where a 5-fold increase was found. Mitochondrial-lysosomal fractions contained 55% of the total kidney interferon. Partial inhibition of proteolytic and HuIFN-α degrading activities at that fraction was also observed. These data, together with our previous findings of accumulation of injected interferon in the mitochondrial-lysosomal fraction of rats and monkeys' kidney cells, provide a further evidence for the main role of the kidney in HuIFN-α degradation.
UR - http://www.scopus.com/inward/record.url?scp=0020441682&partnerID=8YFLogxK
U2 - 10.1089/jir.1982.2.301
DO - 10.1089/jir.1982.2.301
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C2 - 7119510
AN - SCOPUS:0020441682
SN - 0197-8357
VL - 2
SP - 301
EP - 308
JO - Journal of Interferon Research
JF - Journal of Interferon Research
IS - 2
ER -