Skip to main content
SpringerLink
Log in

Immunocytochemical Characterization of Lung Macrophage Surface Phenotypes and Expression of Cytokines in Acute Experimental Silicosis in Mice

  • Published:
The Histochemical Journal Aims and scope Submit manuscript

Abstract

The expression of the surface phenotypical profile and the cytokines TNF-α and IL-1β from murine lung macrophages was studied in parenchymal lung tissue and bronchoalveolar fluid of mice, over a 2-week period, following a single intratracheal instillation of silica. The acute inflammatory reaction, confirmed by a significant augmentation of four times the control values of the number of macrophages recovered by lavage from experimental animals, was followed by organized granulomas in the interstitium. The immunohistochemical analysis of lung tissue sections after silica instillation demonstrated the increased alveolar and interstitial tissue expression of all surface antigens and cytokines studied, mainly Mac-1, F4/80 antigens, TNF-α and IL-1β, which were occasionally observed in normal uninjected and saline-treated mice. These findings show that, after silica instillation, the expression of surface phenotypical markers of lung macrophages increased, and this change was concomitantly associated with an increased expression of the cytokines TNF-α and IL-1β. These changes support the conclusion that an influx of the newly recruited and activated macrophage population, with a different phenotype, is induced by treatment during inflammation. The populational changes involve difference in functional activity and enhance TNF-α and IL-1β expression. These cytokines, produced in the silicosis-induced inflammatory process, are associated with the development of fibrosis and may contribute to disease severity. © 1998 Chapman & Hall

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adamson, I.Y.R. & Bowden, D.H. (1984) Role of polymorphonuclear leukocytes in silica-induced pulmonary fibrosis. Am. J. Pathol. 117, 37-43.

    Google Scholar 

  • Antonini, J.M., van Dyke, K., Ye, Z., Dimatteo, M. & Reasor M.J. (1994) Introduction of luminol-dependent chemiluminescence as a method to study silica inflammation in the tissue and phagocytic cells of rat lung. Environ. Health Perspect. 102, 37-42.

    Google Scholar 

  • Austyn, J.M. & Gordon, S. (1981) A monoclonal antibody directed specifically against the mouse macrophage. Eur. J. Immunol. 11, 805-15.

    Google Scholar 

  • Bilyk, N. & Holt, P.G. (1991) The surface phenotypic characterization of lung macrophages in C3H/HeJ mice. Immunology 74, 645-51.

    Google Scholar 

  • Bissonnette, E. & Rola-pleszczynski, M. (1989) Pulmonary inflammation and fibrosis in a murine model of asbestosis and silicosis: possible role of tumor necrosis factor. Inflammation 13, 329-39.

    Google Scholar 

  • Breel, M., van der Ende, M., Sminia, T. & Kraal, G. (1988) Subpopulations of lymphoid and non-lymphoid cells in bronchus-associated lymphoid tissue (BALT) of the mouse. Immunology 63, 657-62.

    Google Scholar 

  • Bowden, D.H., Hedgecock, C. & Adamson, I.Y.R. (1989) Silica-induced pulmonary fibrosis involves the reaction of particles with interstitial rather than alveolar macrophages. J. Pathol. 158, 73-80.

    Google Scholar 

  • Calhoun, W. J. & Salisbury, S.M. (1989) Heterogeneity in cell recovery and superoxide production in buyant, density-defined subpopulations of human alveolar macrophages from healthy volunteers and sarcoidosis patients. J. Lab. Clin. Med. 114, 682-90.

    Google Scholar 

  • Chu, H.W., Wang, J.M., Boutet, M. & Laviolette, M. (1996) Tumor necrosis factor-á and Interleukin-1α expression in a murine model of allergic bronchopulmonary aspergillosis. Lab. Anim. Sci. 46, 42-7.

    Google Scholar 

  • Carre, P.H., Gossart, S., Rami, J., Cambon, C. & Pipy, B. (1994) Early overexpression of the TNF alpha and Interleukin 1 beta genes by alveolar macrophages in silica-treated rats. Am. J. Resp. Crit. Care Med. 149, 1026A.

    Google Scholar 

  • Dethloff, L.A., Gilmore, L.B., Gladen, B.C., George, G., Chabra, R.S. & Hook, G.E.R. (1986) Effects of silica on the composition of the pulmonary extracellular lining. Toxicol. Appl. Pharmacol. 84, 66-83.

    Google Scholar 

  • Dianarello, C.A. (1989) Interleukin-1 and its biologically related cytokines. Adv. Immunol. 44, 153-205.

    Google Scholar 

  • Driscoll, K.E.R., Lindenschmidt, C., Maurer, J.K., Higgins, J.M., & Ridder, G. (1990a) Pulmonary response to silica or titanium dioxide: inflammatory cells, alveolar macrophage-derived cytokines, and histopathology. Am. J. Respir. Cell. Mol. Biol. 2, 381-90.

    Google Scholar 

  • Driscoll, K.E., Maurer, J.K., Lindenschmidt, R.C., Romberger, D., Rennard, S. I. & Crosby, L. (1990b) Respiratory tract responses to dust: relationship between dust burden, lung injury, alveolar macrophage fibronectin release, and the development of pulmonary fibrosis. Toxicol. Appl. Pharmacol. 106, 88-101.

    Google Scholar 

  • Erlandsen, S.L., Hasslen, S.R. & Nelson, R.D. (1993) Detection and spatial distribution of the β2-integrin (Mac-1) and L-Selectin (LECAM-1) adherence receptors on human neutrophils by high-resolution field emission SEM. J. Histochem. Cytochem. 41, 327-33.

    Google Scholar 

  • Frigeri, L.G. & Liu, F.T. (1992) Surface expression of functional IgE binding protein, an endogen lectin, on mast cells and macrophages. J. Immunol. 148, 861-67.

    Google Scholar 

  • Gant, V.A. & Hamblin, A.S. (1985) Human bronchoalveolar macrophage heterogeneity demonstrated by histochemistry, surface markers and phagocytosis. Clin. Exp. Immunol. 60, 539-45.

    Google Scholar 

  • Gordon, S., Crocker, P.R., MORRIS, L., Lee, S.H., Perry, V.H. & Hume, D.A. (1986) Localization and function of tissue macrophages. Ciba Found. Symp. 118, 54-67.

    Google Scholar 

  • Gossart, S., Cambon, C., Orfila, C., Seguelas, M.H., Lepert, J.C., Rami, J., CarrÉ, P.H. & Pipy, B. (1996) Reactive oxygen intermediates as regulators of TNF-α production in rat lung inflammation induced by silica. J. Immunol. 156, 1540-8.

    Google Scholar 

  • Hendrzak, J.A. & Morahan, P.S. (1992) Importance of resident peritoneal macrophages in the early inflammatory response to herpes simplex virus type 2 infection. FASEB J. 6, A1714.

    Google Scholar 

  • Hildemann, S., Hammer, C. & Krombach, F. (1992) Heterogeneity of alveolar macrophages in experimental silicosis. Environ. Health Perpect. 97, 53-57.

    Google Scholar 

  • Hirsch, S., Austyn, J.M. & Gordon, S. (1981) Expression of the macrophage-specific antigen F4/80 during differentiation of mouse bone marrow cells in culture. J. Exp. Med. 154, 713-25.

    Google Scholar 

  • Ho, M.K. & Springer, T.A. (1982) Mac-2, a novel 32000 mw mouse macrophage subpopulation antigen defined by monoclonal antibodies. J. Immunol. 128, 1221-8.

    Google Scholar 

  • Hocking, W.G. & Golde, W.D. (1979) The pulmonary alveolar macrophage. Part 1. N. Engl. J. Med. 30, 580-7.

    Google Scholar 

  • Hume, D.A., Perry, V.H. & Gordon, S. (1984) The mononuclear phagocyte system of the mouse defined by immunohistological localisations of antigen F4/80: Macrophages associated with epithelia. Anat. Rec. 210, 503-12.

    Google Scholar 

  • Johard, U., Eklund, A., Hed, J. & Lundahl, J. (1993) Terpenes enhance metabolic activity and alter expression of adhesion molecules (Mac-1 and L-selectin) on human granulocytes. Inflammation 4, 499-509.

    Google Scholar 

  • Kasper, M. & Hughes, R.C. (1996) Immunocytochemical evidence for a modulation of galectin 3 (Mac-2), a carbohydrate binding protein, in pulmonary fibrosis. J. Pathol. 179, 309-16.

    Google Scholar 

  • Kraal, G., Rep, M. & Janse, M. (1987) Macrophages in T and B cell compartments and other tissue macrophages recognized by monoclonal antibody MOMA-2. An immunohistochemical study. Scand. J. Immunol. 26, 653-61.

    Google Scholar 

  • Leenen, P.J.M., De Bruijn, M.F.T.R., Voerman, J.S.A., Campbell, P.A. & van Ewijk, W. (1994) Markers of mouse macrophage development detected by monoclonal antibodies. J. Immunol. Meth. 174, 5-19.

    Google Scholar 

  • Lotz, M.M., Andrews, C.W., Korzelius, C.A. Lee, E.C., Steele, G.D., Clarke, A. & Mercurio, A.M. (1993) Decreased expression of Mac-2 (carbohydrate binding protein 35) and loss of its nuclear localization are associated with the neoplastic progression of colon carcinoma. Proc. Natl. Acad. Sci. USA 90, 3466-70.

    Google Scholar 

  • Menson, E.N. & Wilson, R.A. (1990) Lung-phase immunity to Schistosoma mansoni: definition of alveolar macrophage phenotypes after vaccination and challenge of mice. Parasite Immunol. 12, 353-66.

    Google Scholar 

  • Miles, P., Bowman, R.L., Jones, W.G., Berry, D.S. & Vallyathan, V. (1994) Changes in alveolar lavage materials and lung microsomal xenobiotic metabolism following exposures to HCl-washed crystalline silica. Toxicol. Appl. Pharmacol. 129, 235-42.

    Google Scholar 

  • Miller, K., Hudspith, B.N. & Meredith, C. (1992) Secretory and accessory cell functions of the alveolar macrophage. Environ. Health Perspect. 97, 85-9.

    Google Scholar 

  • Mori, H., Tanaka, H., Kawada, K., Nagai, H. & Koda, A. (1995) Suppressive effects of tranilast on pulmonary fibrosis and activation of alveolar macrophages in mice treated with bleomycin: role of alveolar macrophages in the fibrosis. Jpn. J. Pharmacol. 67, 279-89.

    Google Scholar 

  • Nibbering, P.H., Leijh, P.C.J. & van Furth, R. (1987a) Quantitative immunocytochemical characterization of mononuclear phagocytes. II. Monocytes and tissue macrophages. Immunology 62, 171-6.

    Google Scholar 

  • Nibbering, P.H., Leijh, P.C.J. & van Furth, R. (1987b) Quantitative immunocytochemical characterization of mononuclear phagocytes. I. Monoblasts, promonocytes, monocytes and peritoneal and alveolar macrophages. Cell. Immunol. 105, 374-85.

    Google Scholar 

  • Nibbering, P.H., Van De Heide G.A. & Van Furth, R. (1989) Macrophages in bronchoalveolar lavagefluid do not represent macrophages in granulomas of the lungs of BCG-infected mice. Agents Actions 26, 132-3.

    Google Scholar 

  • Oghiso, Y. & Kubota, Y. (1987) Interleukin 1 production and accessory cell function of rat alveolar macrophages exposed to mineral dust particles. Microbiol. Immunol. 31, 275-87.

    Google Scholar 

  • Piguet, P.F., Collart, M.A., Grau, G.E., Sappino, A.P. & Vassalli, P. (1990) Requirement of tumour necrosis factor for development of silica-induced pulmonary fibrosis. Nature 344, 245-7.

    Google Scholar 

  • Plasman, N. & Vray, B. (1994) Immunophenotyping of murine peritoneal macrophages and lymphocytes by flow cytometry. J. Immunol. Methods 174, 123-31.

    Google Scholar 

  • Reiser, K.M., Westerberg, T.W., Haschek, W.M. & Last, J.A. (1983) Experimental silicosis: II. Long-term effects of intratracheally instilled quartz on collagen metabolism and morphologic characteristics of rat lungs. Am. J. Pathol. 110, 30-41.

    Google Scholar 

  • Rutherford, M. S., Witsel, A. & Shook, L.B. (1993) Mechanisms generating functionally heterogeneous macrophages: Chaos revisited. J. Leukocyte Biol. 53, 602-13.

    Google Scholar 

  • Sarih, M., Souvannavong, V., Brown, S.C. & Adam, A. (1993) Silica induces apoptosis in macrophages and the release of interleukin-1á and interleukin-1β. J. Leukocyte Biol. 54, 407-13.

    Google Scholar 

  • Schollmeier, K. (1990) Immunological and pathophysiologic role of tumor necrosis factor. Am. J. Respir. Cell. Mol. Biol. 3, 13-20.

    Google Scholar 

  • Shellito, J. & Kaltreider, H.B. (1985) Heterogeneity of immunologic function among subfractions of normal rat alveolar macrophages. II. Activation as determinant of functional activity. Am. Rev. Respir. Dis. 131, 678-83.

    Google Scholar 

  • Springer, T., Galfre, G., Secher, D.S. & Milstein, C. (1979) Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur. J. Immunol. 9, 301-6.

    Google Scholar 

  • Walker, E.B., Akporiaye, E.T., Warner, N.L. & Stewart, C.C. (1985) Characterization of subsets of bone marrow-derived macrophages by flow cytometry analysis. J. Leukocyte Biol. 37, 121-136.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. UPRES EA-2405, CHU Rangueil, 31403, Toulouse Cedex 4, France

    C. Orfila, J. C. Lepert, S. Gossart, M. F. Frisach, C. Cambon & B. Pipy

Authors
  1. C. Orfila
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. C. Lepert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Gossart
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. F. Frisach
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. Cambon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B. Pipy
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Orfila, C., Lepert, J.C., Gossart, S. et al. Immunocytochemical Characterization of Lung Macrophage Surface Phenotypes and Expression of Cytokines in Acute Experimental Silicosis in Mice. Histochem J 30, 857–867 (1998). https://doi.org/10.1023/A:1003485312164

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1003485312164

Keywords

Search

Navigation