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. 1978 Aug 1;148(2):435–450. doi: 10.1084/jem.148.2.435

Secretion of lysosomal hydrolases by stimulated and nonstimulated macrophages

PMCID: PMC2184949  PMID: 29935

Abstract

Peritoneal macrophages were obtained from untreated mice and from mice treated with thioglycollate medium (TA), proteose peptone medium (PP), or a suspension of streptococcus A cell wall material (SA). The biochemical and secretory properties of these cells in long term cultures (up to 2 wk) were compared. TA-elicited macrophages contained more protein, lactate dehydrogenase, lysosomal hydrolases, and in particular, more plasminogen activator than the other cells studied. All types of macrophages studied were found to release considerable amounts of lysosomal hydrolases (beta-glucuronidase, N-acetyl-beta- glucosaminidase, alpha-mannosidase, and acid phosphatase) into the medium. Release was independent of phagocytosis and must, therefore, be regarded as true secretion. In both elicited and nonelicited macrophages, the rates of lysosomal enzyme secretion were virtually identical in the presence and in the absence of serum, and they were not enhanced by increasing serum concentrations. Lysosomal enzyme secretion in macrophages appears to depend on protein synthesis, since it was blocked by low concentrations of cycloheximide which neither affected cell viability nor lowered the intracellular enzyme levels. The amounts of lysosomal hydrolases secreted were highest in TA- elicited macrophages. The rates of secretion of PP- or SA-elicited and of nonelicited macrophages were about one-fourth of that of the TA- elicited cells. This difference, although significant, is much smaller than that observed for the secretion of plasminogen activator which was 20-50 times higher in TA-elicited cells. Acid glycosidases were also found in the peritoneal lavage media used for cell harvesting from both treated and nontreated mice. This indicates that active secretion of lysosomal hydrolases may be an in vivo property of the macrophage.

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Selected References

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  1. Baggiolini M., Hirsch J. G., De Duve C. Further biochemical and morphological studies of granule fractions from rabbit heterophil leukocytes. J Cell Biol. 1970 Jun;45(3):586–597. doi: 10.1083/jcb.45.3.586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bentley C., Bitter-Suermann D., Hadding U., Brade V. In vitro synthesis of factor B of the alternative pathway of complement activation by mouse peritoneal macrophages. Eur J Immunol. 1976 Jun;6(6):393–398. doi: 10.1002/eji.1830060604. [DOI] [PubMed] [Google Scholar]
  3. Bowers W. E. Lysosomes in rat thoracic duct lymphocytes. J Exp Med. 1972 Dec 1;136(6):1394–1403. doi: 10.1084/jem.136.6.1394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bretz U., Baggiolini M. Biochemical and morphological characterization of azurophil and specific granules of human neutrophilic polymorphonuclear leukocytes. J Cell Biol. 1974 Oct;63(1):251–269. doi: 10.1083/jcb.63.1.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. COHN Z. A., BENSON B. THE DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES. MORPHOLOGY, CYTOCHEMISTRY, AND BIOCHEMISTRY. J Exp Med. 1965 Jan 1;121:153–170. doi: 10.1084/jem.121.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Colman G., Williams R. E. The cell walls of streptococci. J Gen Microbiol. 1965 Dec;41(3):375–387. doi: 10.1099/00221287-41-3-375. [DOI] [PubMed] [Google Scholar]
  7. DE DUVE C., PRESSMAN B. C., GIANETTO R., WATTIAUX R., APPELMANS F. Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem J. 1955 Aug;60(4):604–617. doi: 10.1042/bj0600604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davies P., Page R. C., Allison A. C. Changes in cellular enzyme levels and extracellular release of lysosomal acid hydrolases in macrophages exposed to group A streptococcal cell wall substance. J Exp Med. 1974 May 1;139(5):1262–1282. doi: 10.1084/jem.139.5.1262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Deutsch D. G., Mertz E. T. Plasminogen: purification from human plasma by affinity chromatography. Science. 1970 Dec 4;170(3962):1095–1096. doi: 10.1126/science.170.3962.1095. [DOI] [PubMed] [Google Scholar]
  10. Dewald B., Touster O. A new alpha-D-mannosidase occurring in Golgi membranes. J Biol Chem. 1973 Oct 25;248(20):7223–7233. [PubMed] [Google Scholar]
  11. Dingle J. T. The secretion of enzymes into the pericellular environment. Philos Trans R Soc Lond B Biol Sci. 1975 Jul 17;271(912):315–324. doi: 10.1098/rstb.1975.0055. [DOI] [PubMed] [Google Scholar]
  12. Gordon S., Todd J., Cohn Z. A. In vitro synthesis and secretion of lysozyme by mononuclear phagocytes. J Exp Med. 1974 May 1;139(5):1228–1248. doi: 10.1084/jem.139.5.1228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. HELMKAMP R. W., GOODLAND R. L., BALE W. F., SPAR I. L., MUTSCHLER L. E. High specific activity iodination of gamma-globulin with iodine-131 monochloride. Cancer Res. 1960 Nov;20:1495–1500. [PubMed] [Google Scholar]
  14. Henson P. M. The immunologic release of constituents from neutrophil leukocytes. II. Mechanisms of release during phagocytosis, and adherence to nonphagocytosable surfaces. J Immunol. 1971 Dec;107(6):1547–1557. [PubMed] [Google Scholar]
  15. Hille M. B., Barrett A. J., Dingle J. T., Fell H. B. Microassay for cathepsin D shows an unexpected effedt of cycloheximide on limb-bone rudiments in organ culture. Exp Cell Res. 1970 Aug;61(2):470–472. doi: 10.1016/0014-4827(70)90476-3. [DOI] [PubMed] [Google Scholar]
  16. Oronsky A., Ignarro L., Perper R. Release of cartilage mucopolysaccharide-degrading neutral protease from human leukocytes. J Exp Med. 1973 Aug 1;138(2):461–472. doi: 10.1084/jem.138.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Page R. C., Davies P., Allison A. C. Pathogenesis of the chronic inflammatory lesion induced by group A streptococcal cell walls. Lab Invest. 1974 May;30(5):568–581. [PubMed] [Google Scholar]
  18. Pantalone R., Page R. C. Enzyme production and secretion by lymphokine-activated macrophages. J Reticuloendothel Soc. 1977 May;21(5):343–357. [PubMed] [Google Scholar]
  19. Poole A. R., Hembry R. M., Dingle J. T. Cathepsin D in cartilage: the immunohistochemical demonstration of extracellular enzyme in normal and pathological conditions. J Cell Sci. 1974 Jan;14(1):139–161. doi: 10.1242/jcs.14.1.139. [DOI] [PubMed] [Google Scholar]
  20. Poole A. R., Hembry R. M., Dingle J. T., Pinder I., Ring E. F., Cosh J. Secretion and localization of cathepsin D in synovial tissues removed from rheumatoid and traumatized joints. An immunohistochemical study. Arthritis Rheum. 1976 Nov-Dec;19(6):1295–1307. doi: 10.1002/art.1780190610. [DOI] [PubMed] [Google Scholar]
  21. Schorlemmer H. U., Allison A. C. Effects of activated complement components on enzyme secretion by macrophages. Immunology. 1976 Nov;31(5):781–788. [PMC free article] [PubMed] [Google Scholar]
  22. Schorlemmer H. U., Bitter-Suermann D., Allison A. C. Complement activation by the alternative pathway and macrophage enzyme secretion in the pathogenesis of chronic inflammation. Immunology. 1977 Jun;32(6):929–940. [PMC free article] [PubMed] [Google Scholar]
  23. Schorlemmer H. U., Davies P., Hylton W., Gugig M., Allison A. C. The selective release of lysosomal acid hydrolases from mouse peritoneal macrophages by stimuli of chronic inflammation. Br J Exp Pathol. 1977 Jun;58(3):315–326. [PMC free article] [PubMed] [Google Scholar]
  24. Tulkens P., Schneider Y. J., Trouet A. The fate of the plasma membrane during endocytosis. Biochem Soc Trans. 1977;5(6):1809–1815. doi: 10.1042/bst0051809. [DOI] [PubMed] [Google Scholar]
  25. Unkeless J. C., Gordon S., Reich E. Secretion of plasminogen activator by stimulated macrophages. J Exp Med. 1974 Apr 1;139(4):834–850. doi: 10.1084/jem.139.4.834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Weissmann G., Goldstein I., Hoffstein S., Chauvet G., Robineaux R. Yin/Yang modulation of lysosomal enzyme release from polymorphonuclear leukocytes by cyclic nucleotides. Ann N Y Acad Sci. 1975 Jun 13;256:222–232. doi: 10.1111/j.1749-6632.1975.tb36049.x. [DOI] [PubMed] [Google Scholar]
  27. Werb Z., Gordon S. Elastase secretion by stimulated macrophages. Characterization and regulation. J Exp Med. 1975 Aug 1;142(2):361–377. doi: 10.1084/jem.142.2.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Werb Z., Gordon S. Secretion of a specific collagenase by stimulated macrophages. J Exp Med. 1975 Aug 1;142(2):346–360. doi: 10.1084/jem.142.2.346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. von Figura K., Kresse H., Meinhard U., Holtfrerich D. Studies on secretion and endocytosis of macromolecules by cultivated skin fibroblasts. Effects of anti-microtubular agents on secretion and endocytosis of lysosomal hydrolases and of sulphated glycosaminoglycans. Biochem J. 1978 Feb 15;170(2):313–320. doi: 10.1042/bj1700313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. von Figura K. Secretion of beta-hexosaminidase by cultured human skin fibroblasts. Kinetics, effect of temperature, cell density, serum concentration and pH. Exp Cell Res. 1978 Jan;111(1):15–21. doi: 10.1016/0014-4827(78)90231-8. [DOI] [PubMed] [Google Scholar]

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