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Cathepsin D activity in human peripheral blood mononuclear leukocytes

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Abstract

To investigate the cellular origins of cathepsin D (CD) in inflammatory lesions, the CD content of lymphocyte subsets, monocytes, and macrophages were compared. Human monocytes, B lymphocytes, CD4+ T lymphocytes, and CDS + T lymphocytes were separated from peripheral blood of normal donors. CD content was 0.13±01μg equivalents of CD per million cells and significant differences between different cell types were not found. To determine the CD content of macrophages, differentiation of peripheral blood monocytes was induced by either in vitro culture or treatment with 4β-phorbol-12-myristate-13-acetate (PMA). Macrophages induced by five-day culture contained four times more CD than unstimulated monocytes, and macrophages induced by 18-h treatment with 20 mg/ml 4β-PMA contained nine times more CD than monocytes treated with 4α-PMA, an inactive stereoisomer of 4β-PMA. These results suggest that macrophages are one of the enriched sources of CD in inflammatory lesions.

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References

  1. Barrett, A. J. 1977. Cathepsin D and other carboxyl proteinases.In Proteinases in Mammalian Cells and Tissues. A. J. Barrett, editor. North-Holland Publishing, Amsterdam. 209–248.

    Google Scholar 

  2. Whitaker, J. N., andJ. M. Seyer, 1979. The sequential limited degradation of bovine myelin basic protein by bovine brain cathepsin D.J. Biol. Chem 254:6959–6963.

    Google Scholar 

  3. Marks, N., andF. Stern. 1975. Inactivation of somatostatin and its analogs by crude and partially purified rat brain extracts.FEBS Lett. 55:220–224.

    Google Scholar 

  4. Benuck, M., A. Grynbaum, andN. Marks. 1977, Breakdown of somatostatin and substance P by cathepsin D purified from calf brain by affinity chromatography.Brain Res. 143:181–185.

    Google Scholar 

  5. Hackenthal, E., R. Hackenthal, andU. Higenfeldt. 1978. Isorenin, pseudorenin, cathepsin D, and renin: A comparative enzymatic study of angiotensin-forrming enzymes.Biochim. Biophys. Act 522:574–588.

    Google Scholar 

  6. Barat, E., A. Patthy, andL. Graf. 1979. Action of cathepsin D on human beta-lipotropin: A possible source of beta-melanotropin.Proc. Natl. Acad. Sci. U.S.A. 76:6120–6123.

    Google Scholar 

  7. Graf, L., A. Dennessey, A. Patthy, A. Grynbaum, N. Marks, andA. Lajtha. 1979. Cathepsin D generated gamma-endorphin from beta-endorphin.Arch. Biochem. Biophys. 193:101–109.

    Google Scholar 

  8. Bazin, S., andA. Delaunay. 1969. Modification of proteolytic enzyme activity in experimental inflammation.In Inflammation Biochemistry and Drug Interactions. A. Bertelli and J. C. Houck, editors, Williams & Wilkins and Excerpta Medica, Baltimore and Amsterdam, 21–28.

    Google Scholar 

  9. Morrison, R. I. G., A. J. Barrett, J. T. Dingle, andD. Prior. 1973. Cathepsins B and D action on human cartilage proteoglycans.Biochim. Biophys. Acta 302:411–419.

    Google Scholar 

  10. Ishikawa, I., G. Cimasoni, andC. Ahmad-Zadeh. 1972. Possible role of lysosomal enzymes in the pathogenesis of periodontitis. A study on cathepsin D in human gingival fluid.Arch. Oral Biol. 17:111–117.

    Google Scholar 

  11. Lah, T., U. Skaleric, J. Babnk, andV. Turk. 1985. Cathepsin D, L and B in inflamed human gingiva.J. Periodont. Res. 20:458–466.

    Google Scholar 

  12. Hallpike, J. F., C. W. M. Adams, andO. B. Bayliss. 1970. Histochemistry of myelin. VIII Proteolytic activity around plaques of multiple sclerosis.Histochem. J. 2:199–208.

    Google Scholar 

  13. Einstein, E. R., J.Csejtey, K. B.Dalal, C. W. M.Adams, O. B.Bayliss, and J. F.Hallpike. Proteolytic activity and basic protein loss in and around multiple sclerosis plaques: Combined biochemical and histochemical observations.J. Neurochem. 19:653–662.

  14. Riekkinen, P. J., J. Clausen, H. J. Frey, T. Fog, andU. K. Rinne. 1970. Acid proteinase activity of white matter and plaques in multiple sclerosis.Acta Neurol. Scand. 46:349–353.

    Google Scholar 

  15. Traugott, U., E. L. Reinherz, andC. S. Raine. 1983. Multiple sclerosis: Distribution of T lymphocyte subsets within active chronic lesions.Science 219:308–310.

    Google Scholar 

  16. Booss, J., M. M. Esiri.W. W. Tourtellotte, andD. Y. Mason. 1983. Immunohistochemical analysis of T lymphocyte subsets in the central nervous system in chronic progressive multiple sclerosis.J. Neurol. Sci. 62:219–232.

    Google Scholar 

  17. Hauser, S. L., A. K. Bahn, F. Gilles, M. Kemp, C. Kerr, andH. L. Weiner. 1986. Immunohistochemical analysis of cellular infiltrate in multiple sclerosis lesions.Ann. Neurol. 19:528–587.

    Google Scholar 

  18. Woodroofe, M. N., A. S. Bellamy, M. Feldmann, A. N. Davison, andM. L. Cuzner. 1986. Immunocytochemical characterization of the immune reaction in the central nervous system in multiple sclerosis.J. Neurol. Sci. 74:135–152.

    Google Scholar 

  19. McCallum, K., M. M. Esiri, W. W. Tourtellotte, andJ. Booss. 1987. T cell subsets in multiple sclerosis: Gradients at plaque borders and differences in nonplaque regions.Brain 110:1297–1308.

    Google Scholar 

  20. Whitaker, J. N., andJ. M. Seyer. 1979. Isolation and characterization of bovine brain cathepsin D.J. Neurochem. 32:325–329.

    Google Scholar 

  21. Cohn, Z. A., andB. Benson. 1965. The in vitro differentiation of mononuclear phagocytes.J. Exp. Med. 121:835–848.

    Google Scholar 

  22. Gidlund, M., A. Orn, P. K. Pattengale, M. Jansson, H. Wigzell, andK. Nilsson. 1981. Natural killer cells kill tumor cells at a given stage or differentiation.Nature 292:848–850.

    Google Scholar 

  23. Guyre, P. M., G. R. Craetree, J. E. Bodwell, andA. Munck. 1981. MLC-conditioned media stimulate an increase in Fc receptors on human macrophages.J, Immunol. 126:668–688.

    Google Scholar 

  24. Celniker, A., andD. O. Lucas. 1985. Cathepsin D in diiferentiating U-937 cells.Fed. Proc. 44:1702 (abstract 7551).

    Google Scholar 

  25. Stefanovic, J., T. Webb, andC. Lapresle. 1962. Etude des cathepsines D et E dans des preparations de polynucleaires demacrophages et de lymphocytes de lapin.Ann. Inst. Pasteur 103:276.

    Google Scholar 

  26. Morland, B., andA. Pedersen. 1979. Cathepsin B activity in stimulated mouse peritoneal macrophages.Lab. Invest. 41:379–384.

    Google Scholar 

  27. Orlowski, M., R. Orlowski, J. C. Chang, E. Wilk, andM. Lesser. 1984. A sensitive procedure for determination of cathepsin D: Activity in alveolar and peritoneal macrophages.Mol. Cell. Biochem. 64:155–162.

    Google Scholar 

  28. Lesser, M., J. C. Chano, andM. Orlowski. 1985. CATHEPSIN B and D activity in stimulated peritoneal macrophages.Mol. Cell. Biochem. 69:67–73.

    Google Scholar 

  29. Hughs, K. T., G. A. Coles, T. R. Harry, andM. Davies. 1981. Some properties of human blood monocyte cell lysate neutral proteinase.Biochim. Biophys. Acta 662:111.

    Google Scholar 

  30. Goto, I., N. Shinno, andY. Kuroiwa. 1986. Proteolytic enzyme activities of macrophages and lymphocytes in neurological diseases.J. Neurol. 233:373–375.

    Google Scholar 

  31. Meller, J., G. Brun Del Re, H. Buerki, H. V. Keller, M. W. Hess, andH. Cottier. 1975. Nonspecific acid esterase activity: A criterion for differentiation of T and B lymphocytes in mouse lymph nodes.Eur. J. Immunol. 5:270–274.

    Google Scholar 

  32. Horowitz, D. A., A. C. Allison, P. Ward, andN. Dight. 1977. Identification of human mononuclear leukocyte subpopulations by esterase staining.Clin. Exp. Immunol. 30:289–298.

    Google Scholar 

  33. Seymour, G. J., H. M. Dockrell, andJ. S. Greenspan. 1978. Enzyme differentiation of lymphocyte subpopulations in sections of human lymph nodes, tonsils, and periodontal disease.Clin. Exp. Immunol. 32:169–178.

    Google Scholar 

  34. Barr, R. D., andS. P. Perry. 1976. Lysosomal acid hydrolyses in human lymphocyte subpopulations.Br. J. Haematol. 32:565–572.

    Google Scholar 

  35. Kulenkampff, J., G. Janossy, andM. F. Breaves. 1977. Acid esterase in human lymphoid cells and leukemic blasts.Br. J. Haematol. 36:231–240.

    Google Scholar 

  36. Tanaka, T. 1979. Biochemical activities of nine lysosomal enzymes in T and non-T lymphocytes.FEBS Lett. 104:161–164.

    Google Scholar 

  37. Golaz, J., A. Steck, andL. Moretta. 1983. Activated T lymphocytes in patients with multiple sclerosis.Neurology 33:1371–1373.

    Google Scholar 

  38. Grayzel, A. I., V. B. Hatcher, andG. S. Lazarus. 1975. Proteinase activity of normal and PHA stimulated human lymphocytes.Cell Immunol. 18:210–219.

    Google Scholar 

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Author notes

  1. Christopher T. Bever Jr.

    Present address: Neurology and Research Services, VAMC, Memphis, Tennessee

  2. John N. Whitaker

    Present address: Department of Neurology, University of Tennessee, Memphis, Tennessee

Authors and Affiliations

  1. Neurology and Research Services, and Department of Neurology, VAMC, Baltimore, Maryland

    Christopher T. Bever Jr., Kerry D. Morgan & John N. Whitaker

  2. Neurology Department and Neurology and Research Services, University of Alabama, Birmingham, Alabama

    Christopher T. Bever Jr., Kerry D. Morgan & John N. Whitaker

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  1. Christopher T. Bever Jr.
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  2. Kerry D. Morgan
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  3. John N. Whitaker
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Bever, C.T., Morgan, K.D. & Whitaker, J.N. Cathepsin D activity in human peripheral blood mononuclear leukocytes. Inflammation 13, 309–316 (1989). https://doi.org/10.1007/BF00914397

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