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A stereological ultrastructural study of stimulated peritoneal macrophages in the germ-free mouse

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Summary

Peritoneal macrophage ultrastructure was analysed stereologically in germ-free mice given a single intraperitoneal injection of sterile, pyrogen-free saline. Thus the stimulant was non-particulate, non-antigenic and inorganic, and effects of immune reactions were minimal. Macrophages were recovered 1, 6, 24 and 72 h after stimulation.

A sequence of structural alterations is reported which may be fundamental to macrophage activation. The plasma membrane and nuclear envelope increased in area within only 1 h of saline injection. During the next 5 h loss of plasma membrane, probably by pinocytosis, caused cellular “rounding” and clear-cut alteration in surface configuration. At the same time lysosome-like granules enlarged but decreased in number. By 24 h most cellular structures and compartments (including the plasma membrane) were enlarged. Morphological evidence of nuclear activation accompanied a rather modest enlargement of the nucleus at this stage. The RER hypertrophied last and must, therefore, be judged sufficient in resident macrophages to support the initial growth response which results after stimulation. Thus hypertrophy was observed eventually in every structure examined. Even the minimally activated macrophages resident in the peritoneum of germ-free mice respond readily to stimulation.

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References

  • Bygrave, F.L.: Mitochondria and the control of intracellular calcium. Biol. Rev. 53, 43–79 (1978)

    Google Scholar 

  • Casley-Smith, J.R.: Endocytosis: the different energy requirements for the uptake of particles by small and large vesicles into peritoneal macrophages. J. Microsc. 90, 15–30 (1969)

    Google Scholar 

  • Cohn, Z.A.: The activation of mononuclear phagocytes: fact, fancy, and future. J. Immunol. 121, 813–816 (1978)

    Google Scholar 

  • Daems, W.Th., Koerten, H.K.: The effects of various stimuli on the cellular composition of peritoneal exudates in the mouse. Cell Tissue Res. 190, 47–60 (1978)

    Google Scholar 

  • Dienstman, S.R., Defendi, V.: Necessary and sufficient conditions for recruitment of macrophages into the cell cycle. Exp. Cell Res. 115, 191–199 (1978)

    Google Scholar 

  • Ehrenreich, B.A., Cohn, Z.A.: Pinocytosis by macrophages. J. reticuloendoth. Soc. 5, 230–242 (1968)

    Google Scholar 

  • Gordon, S., Cohn, Z.A.: The macrophage. Int. Rev. Cytol. 36, 171–214 (1973)

    Google Scholar 

  • Gurdon, J.B., Woodland, H.R.: The cytoplasmic control of nuclear activity in animal development. Biol. Rev. 43, 233–267 (1968)

    Google Scholar 

  • Harris, J.R.: The biochemistry and ultrastructure of the nuclear envelope. Biochim. Biophys. Acta 515, 55–104 (1978)

    Google Scholar 

  • Jungi, T.W., McGregor, D.D.: Impaired chemotactic responsiveness of macrophages from gnotobiotic rats. Infect. Immun. 19, 553–561 (1978)

    Google Scholar 

  • Karnovsky, M.L., Lazdins, J., Simmons, S.R.: Metabolism of activated mononuclear phagocytes at rest and during phagocytosis. In: Mononuclear Phagocytes (van Furth, R., ed.), pp. 423–439. Oxford, London, Edinburgh, Melbourne: Blackwell 1975

    Google Scholar 

  • Mayhew, T.M., Williams, M.A.: A morphometric study of the rat peritoneal macrophage following stimulation in vivo. J. Anat. (Lond.) 108, 602 (1971a)

    Google Scholar 

  • Mayhew, T.M., Williams, M.A.: A comparison of two sampling procedures for stereological analysis of cell pellets. J. Microsc. 94, 195–204 (1971b)

    Google Scholar 

  • Mayhew, T.M., Williams, M.A.: A quantitative morphological analysis of macrophage stimulation. I. A study of subcellular compartments and of the cell surface. Z. Zellforsch. 147, 567–588 (1974a)

    Google Scholar 

  • Mayhew, T.M., Williams, M.A.: A quantitative morphological analysis of macrophage stimulation. II. Changes in granule number, size and size distributions. Cell Tissue Res. 150, 529–543 (1974b)

    Google Scholar 

  • Nagl, W.: Nuclear structures during cell cycles. In: Mechanisms and Control of Cell Division (Rost, T.L., Gifford, E.M., Jr., eds.), pp. 147–193. Stroudsburg, Pennsylvania: Dowden, Hutchinson and Ross, Inc. 1977

    Google Scholar 

  • Nath, I., Poulter, L.W., Turk, J.L.: Effect of lymphocyte mediators on macrophages in vitro. A correlation of morphological and cytochemical changes. Clin. Exp. Immunol. 13, 455–466 (1973)

    Google Scholar 

  • Perkins, E.H., Nettesheim, T., Morita, T., Walburg, H.E., Jr.: The engulfing potential of peritoneal phagocytes of conventional and germ-free mice. In: The Reticuloendothelial System and Atherosclerosis (Diluzio, N.R., Paoletti, R., eds.), pp. 175–187. New York: Plenum Press 1967

    Google Scholar 

  • Ringertz, N.R., Bolund, L.: Reactivation of chick erythrocyte nuclei by somatic cell hybridization. Int. Rev. Exp. Pathol. 13, 83–116 (1974)

    Google Scholar 

  • Robertson, T.A., Papadimitriou, J.M., Walters, M., Wolman, M.: Effects of exposure of murine peritoneal exudate and resident macrophages to high molecular levan: A morphological study. J. Pathol. 123, 157–164 (1977)

    Google Scholar 

  • Ryan, G.B., Majno, G.: Acute inflammation. Am. J. Path. 86, 185–276 (1977)

    Google Scholar 

  • Steinman, R.M., Brodie, S.E., Cohn, Z.A.: Membrane flow during pinocytosis. A stereologic analysis. J. Cell Biol. 68, 665–687 (1976)

    Google Scholar 

  • Szego, C.M.: The lysosome as a mediator of hormone action. Recent Progr. Horm. Res. 30, 171–233 (1974)

    Google Scholar 

  • Tulkens, P., Schneider, Y.J., Trouet, A.: Flow and shuttle of plasma membrane during endocytosis. Acta Biol. Med. Ger. 36, 1681–1690 (1977)

    Google Scholar 

  • Unanue, E.R.: Secretory function of mononuclear phagocytes. A Review. Am. J. Path. 83, 396–418 (1976)

    Google Scholar 

  • van Furth, R., Thompson, J.: Review of the origin and kinetics of the promonocytes, monocytes, and macrophages and a brief discussion of the mononuclear phagocyte system. Ann. Inst. Pasteur 120, 337–355 (1971)

    Google Scholar 

  • van Furth, R., Cohn, Z.A., Hirsch, J.G., Humphrey, J.H., Spector, W.G., Langevoort, H.L.: The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells. Bull. W.H.O. 46, 845–852 (1972)

    Google Scholar 

  • van Waarde, D., Hulsing-Hesselink, E., van Furth, R.: Humoral regulation of monocytosis during an acute inflammatory reaction. In: Mononuclear Phagocytes (van Furth, R., ed.), pp. 205–220. Oxford, London, Edinburgh, Melbourne: Blackwell 1975

    Google Scholar 

  • White, A., Handler, P., Smith, E.L.: Principles of Biochemistry (fifth edition). New York, San Francisco, St. Louis, Sydney, Toronto: McGraw Hill Book Campany 1973

    Google Scholar 

  • Williams, M.A., Mayhew, T.M.: Quantitative microscopical studies of the mouse peritoneal macrophage following stimulation in vivo. Z. Zellforsch. 140, 187–202 (1973)

    Google Scholar 

  • Woodward, B.: The use of the germ-free mouse in the study of macrophage stimulation in vivo. J. Physiol. (Lond.) 259, 3–4P (1976)

    Google Scholar 

  • Woodward, B.: The peritoneal leukocytes of the germ-free mouse. Experientia 34, 1638–1639 (1978a)

    Google Scholar 

  • Woodward, B.: A stereological ultrastructural study of peritoneal macrophages from germ-free and conventionally-reared mice. Cell Tissue Res. 192, 157–166 (1978b)

    Google Scholar 

Download references

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This work was supported by a scholarship received from the Association of Commonwealth Universities.

I am grateful to Professor R. Barer for his helpful criticism of this manuscript. I also thank Dr. G.H. Cope and Dr. T.M. Mayhew for much thoughtful consideration given to this study and Mr. O. Illman, Animal House Curator, for his aid. The technical assistance of Mr. G.W. Peace, Mrs. M. Hollingworth and Mr. M. Fenner is gratefully acknowledged.

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Woodward, B. A stereological ultrastructural study of stimulated peritoneal macrophages in the germ-free mouse. Cell Tissue Res. 200, 299–309 (1979). https://doi.org/10.1007/BF00236422

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