1887

Abstract

SUMMARY

The metabolic fate of human leukocyte interferon (HuIFN-α) was studied after intravenous injection into rats and cynomolgus monkeys. At various intervals the animals were sacrificed and the HuIFN-α content determined in serum and various tissues. HuIFN-α 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 (15000 ) had a high HuIFN-α content. It was also found that HuIFN-α 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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-59-1-39
1982-03-01
2021-10-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/59/1/JV0590010039.html?itemId=/content/journal/jgv/10.1099/0022-1317-59-1-39&mimeType=html&fmt=ahah

References

  1. Barrett A. J., Heath M. F. 1977; Lysosomal enzymes. In Lysosomes: a Laboratory Handbook 2nd edn pp 19–45 Edited by Dingle J. T. Amsterdam: Elsevier/North-Holland Biomedical Press;
    [Google Scholar]
  2. Bocci V., Russi-Sorce M., Cirri G., Rita G. 1968; Role of liver in the inactivation of interferon. Proceedings of the Society for Experimental Biology and Medicine 128:62–65
    [Google Scholar]
  3. Bocci V., Pacini A., Pessina G. P., Bargigli V., Russi M. 1977; Metabolism of interferon: hepatic clearance of native and desialylated interferon. Journal of General Virology 35:525–534
    [Google Scholar]
  4. Cantell K., Hirvonen S. 1977; Preparation of human leukocyte interferon for clinical use. Texas Reports on Biology and Medicine 35:138–141
    [Google Scholar]
  5. Cantell K., Pyhälä L. 1973; Circulating interferon in rabbits after administration of human interferon by different routes. Journal of General Virology 20:97–104
    [Google Scholar]
  6. Cantell K., Pyhälä L. 1976; Pharmacokinetics of human leukocyte interferon. Journal of Infectious Diseases 133:A-6–A-12
    [Google Scholar]
  7. Emödi G., Just M., Hernandez R., Hirt H. R. 1975a; Circulating interferon in man after administration of exogenous human leukocyte interferon. Journal of the National Cancer Institute 54:1045–1049
    [Google Scholar]
  8. Emödi G., Rufli T., Just M., Hernandez R. 1975b; Human interferon therapy for herpes zoster in adults. Scandinavian Journal of Infectious Diseases 7:1–5
    [Google Scholar]
  9. Fantes K. H. 1973; Purification and physico-chemical properties of interferon. In Interferons and Interferon Inducers pp 171–200 Edited by Finter N. B. Amsterdam: North-Holland;
    [Google Scholar]
  10. Hilfenhaus J., Karges H. E., Weinmann E., Barth R. 1975; Effect of administered human interferon on experimental rabies in monkeys. Infection and Immunity 11:1156–1158
    [Google Scholar]
  11. Hilfenhaus J., Weinmann E., Majer M., Barth R., Jaeger J. 1977; Post-exposure administration of human interferon to rabies-infected monkeys. Journal of Infectious Diseases 135:846–851
    [Google Scholar]
  12. Johnson D., Lardy H. 1967; Isolation of liver or kidney mitochondria. Methods in Enzymology 10:94–96
    [Google Scholar]
  13. Lowry O. H., Rosebrough N. J., Farr A. L., Randall R. J. 1951; Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193:265–275
    [Google Scholar]
  14. Maunsbach A. B. 1969; Functions of lysosomes in kidney cells. In Lysosomes in Biology and Pathology pp 115–154 Edited by Dingle J. T., Fell H. B. Amsterdam & London: North Holland;
    [Google Scholar]
  15. Maunsbach A. B. 1974; Isolation of kidney lysosomes. Methods in Enzymology 31:330–339
    [Google Scholar]
  16. Mogensen K. E., Cantell K. 1977; Production and preparation of human leukocyte interferon. Pharmacology and Therapeutics 1:369–383
    [Google Scholar]
  17. Mogensen K. E., Pyhala L., Torma E., Cantell K. 1974; No evidence for carbohydrate moiety affecting the clearance of circulating human leukocyte interferon in rabbits. Acta Pathologica et Microbiologica Scandinavica B82:305–310
    [Google Scholar]
  18. Pacini A., Bocci V., Muscettola M., Paulesu L., Pessina G. P., Russi M. 1980; Increased interferonuria in maleate-treated rabbits. In Interferon: Properties and Clinical Uses pp 291–298 Edited by Khan A., Hill N. O., Dorn G. L. Dallas: Leland Fikes Foundation Press;
    [Google Scholar]
  19. Skreko F., Zajac I., Bahnsen H. P., Haff R. F., Cantell K. 1973; The kinetics of human interferon clearance in gibbons. Proceedings of the Society for Experimental Biology and Medicine 142:946–947
    [Google Scholar]
  20. Tilles J. G., Finland M. 1968; Microassay for human and chick cell interferons. Applied Microbiology 16:1706–1708
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-59-1-39
Loading
/content/journal/jgv/10.1099/0022-1317-59-1-39
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error