Immunophenotypic and Ultrastructural Differentiation and Maturation of Nonlymphoid Dendritic Cells in Osteopetrotic (op) Mice with the Total Absence of Macrophage Colony Stimulating Factor Activity

  • Kiyoshi Takahashi
  • Makoto Naito
  • Yuki Morioka
  • Leonard D. Shultz
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 329)


To examine the effect of macrophage colony stimulating factor (M-CSF) or CSF-1 on the differentiation and maturation of nonlymphoid dendritic cells (DCs) in vivo, the osteopetrotic mouse (op/op mouse) is a useful tool. This is because the op mutation is shown to be a defect in the coding region of the macrophage colony stimulating factor (Csfm) gene and because CSF-1 produced is nonfunctional, although this mouse does produce Csfm messenger RNA at normal levels.1 This mutation is transmitted by an autosomal recessive trait and homozygous (op/op) mice are characterized by the absence of incisors, a distinctly domed skull, a short tail, and a small body size.2 These phenotypic abnormalities become evident by ten days after birth. In addition to a marked reduction of osteoclasts, deficiencies of monocytes and monocyte-derived macrophages occur in op/op mice.3,4 All these result from the lack of CSF-1 activity. In a recent study, we found immature macrophages in various organs and tissues of op/op mice, suggesting that these CSF-1-independent macrophages are derived from granulocyte/macrophage colony forming cells (GM-CFCs) or earlier hematopoietic progenitors.5 However, little is known about the DCs of op/op mice, including interdigitating cells (IDCs) in the thymus or peripheral lymphoid tissues, epidermal Langerhans cells (LCs), or indeterminate dendritic cells (IDDCs).


Autosomal Recessive Trait Birbeck Granule Peripheral Lymphoid Tissue Epidermal Sheet Thymic Medulla 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    H. Yoshida, S-I. Hayashi, T. Kunisada, M. Ogawa, S. Nishikawa, H. Okamura, T. Sudo, L.D. Shultz, and S-I. Nishikawa, The murine mutation “osteopetrosis” (op is a mutation in the coding region of the macrophage colony stimulating factor (Csfm) gene, Nature, 345: 442 (1990).PubMedCrossRefGoogle Scholar
  2. 2.
    S.C. Marks. Morphological evidence of reduced bone resorption in osteopetrotic (op) mice, Am. J. Anat. 163: 157 (1982).PubMedCrossRefGoogle Scholar
  3. 3.
    W. Wiktor-Jedrzejczak, A. Ahmed, C. Szczylik, and R.R. Skelly, Hematological characterization of congenital osteopetrosis in op/op mouse, Proc. Natl. Acad. Sci. USA, 87: 4828 (1990).PubMedCrossRefGoogle Scholar
  4. 4.
    H. Kodama, A. Yamazaki, M. Nose, S. Niida, Y. Ohgame, M. Abe, M. Kumegawa, and T. Suda, Congenital osteoclast deficiency in osteopetrotic (op/op) mice is cured by injections of macrophage colony-stimulating factor. J. Exp. Med. 173: 269 (1991).PubMedCrossRefGoogle Scholar
  5. 5.
    M. Naito, S-I. Hayashi, H. Yoshida, S-I. Nishikawa, L.D. Shultz, and K. Takahashi, Abnormal differentiation of tissue macrophage populations in ‘osteopetrosis’ (op) mice defective in the production of macrophage colony-stimulating factor, Am. J. Pathol. 139: 657 (1991).PubMedGoogle Scholar
  6. 6.
    D.A. Hume, A.P. Robinson, G.G. MacPherson, and S. Gordon, The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80, J. Exp. Med. 158: 1522 (1983).PubMedCrossRefGoogle Scholar
  7. 7.
    D.A. Hume, J.F. Loutit, and S. Gordon, The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80: Macrophages of bone and associated connective tissue, J. Cell Sci, 66: 189 (1984).PubMedGoogle Scholar
  8. 8.
    U. Malorny, E. Michels, and C. Sorg, A monoclonal antibody against an antigen present on mouse macrophages and absent from monocytes, Cell Tissue Res, 243: 421 (1986).PubMedCrossRefGoogle Scholar
  9. 9.
    G. Kraal, M. Breel, M. Janse, and G. Bruin, Langerhans’ cells, veiled cells, and interdigitating cells in the mouse recognized by a monoclonal antibody, J. Exp. Med. 163: 981 (1986).PubMedCrossRefGoogle Scholar
  10. 10.
    M. Breel, R.E. Mebius, and G. Kraal, Dendritic cells of the mouse recognized by two monoclonal antibodies, Eur. J. Immunol. 17: 1555 (1987).Google Scholar
  11. 11.
    T. Maruyama, S. Tanaka, B. Bozoky, F. Kobayashi, and H. Uda, New monoclonal antibody that specifically recognizes murine interdigitating cells and Langerhans cells, Lab. Invest. 61: 98 (1989).PubMedGoogle Scholar
  12. 12.
    A. Bhattacharya, M.E. Dorf, and T.A. Springer, A shared alloantigentic determinants on Ia antigens encoded by the I-A and I-E subregions: Evidence for I region gene duplication, J. Immunol. 127: 2488 (1981).PubMedGoogle Scholar
  13. 13.
    I.C. Mackenzie, and C.A. Squier, Cytochemical identification of ATPase-positive Langerhans cells in EDTA-separated sheets of mouse epidermis, Br. J. Dermatol. 92: 523 (1975).PubMedCrossRefGoogle Scholar
  14. 14.
    M.B. Chaker, M.D. Tharp, and P.R. Bergstresser, Rodent epidermal Langerhans cells demonstrate greater histochemical specificity for ADP than for ATP and AMP, J. Invest. Dermatol. 82: 496 (1984).PubMedCrossRefGoogle Scholar
  15. 15.
    E.C.M. Hoefsmit and R.H.J. Beelen, The expression of antigen F4/80 and Ia on peritoneal macrophages in normal and BCG-immunized mice, in: “Mononuclear Phagocytes, Characterization, Physiology, and Function,” R. van Furth, ed., Martinus Nijhoff Publishers, Dordrecht (1985).Google Scholar
  16. 16.
    C. Heufler, F. Koch, and G. Schuler, Granulocyte/macrophage colony-stimulating factor and interleukin-1 mediate the maturation of murine epidermal Langerhans cells into potent immunostimulatory dendritic cells, J. Exp. Med. 167: 700 (1988).PubMedCrossRefGoogle Scholar
  17. 17.
    G.G. MacPherson, S. Fossum, and B. Harrison, Properties of lymph-borne (veiled) dendritic cells in culture. II. Expression of the IL-2 receptor: Role of GM-CSF, Immunology 68: 108 (1989).PubMedGoogle Scholar
  18. 18.
    S. Markowicz and E.G. Engleman, Granulocyte-macrophage colony-stimulating factor promotes differentiation and survival of human peritoneal blood dendritic cells in vitro, J. Clin. Invest. 85: 955 (1990)PubMedCrossRefGoogle Scholar
  19. 19.
    M.D. Witmer-Pack, W. Olivier, J. Valinsky, G. Schuler, and R.M. Steinman, Granulocyte/macrophage colony-stimulating factor is essential for the viability and function of cultured murine epidermal Langerhans cells, J. Exp. Med. 166: 1484 (1987).PubMedCrossRefGoogle Scholar
  20. 20.
    R.M. Steinman, S. Koide, M. Witmer, M. Crowley, N. Bhadwaj, P. Freudenthal, J. Young, and K. Inaba, The sensitization phase of T-cell-mediated immunity, Ann. N.Y. Acad. Sci, 546: 80 (1988).PubMedCrossRefGoogle Scholar
  21. 21.
    K. Akagawa. Differentiation of human monocytes and cytokines, J. Jpn. Soc. RES. 32: 174 (1992) (in Japanese).Google Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Kiyoshi Takahashi
    • 1
  • Makoto Naito
    • 1
  • Yuki Morioka
    • 1
  • Leonard D. Shultz
    • 2
  1. 1.Second Department of PathologyKumamoto University School of MedicineKumamotoJapan
  2. 2.The Jackson LaboratoryBar HarborMaineUSA

Personalised recommendations