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Am J Pathol. Aug 1996; 149(2): 559–574.
PMCID: PMC1865316

Effects of macrophage colony-stimulating factor on macrophages and their related cell populations in the osteopetrosis mouse defective in production of functional macrophage colony-stimulating factor protein.

Abstract

The development of macrophage populations in osteopetrosis (op) mutant mice defective in production of functional macrophage colony-stimulating factor (M-CSF) and the response of these cell populations to exogenous M-CSF were used to classify macrophages into four groups: 1) monocytes, monocyte-derived macrophages, and osteoclasts, 2) MOMA-1-positive macrophages, 3) ER-TR9-positive macrophages, and 4) immature tissue macrophages. Monocytes, monocyte-derived macrophages, osteoclasts in bone, microglia in brain, synovial A cells, and MOMA-1- or ER-TR9-positive macrophages were deficient in op/op mice. The former three populations expanded to normal levels in op/op mice after daily M-CSF administration, indicating that they are developed and differentiated due to the effect of M-CSF supplied humorally. In contrast, the other cells did not respond or very slightly responded to M-CSF, and their development seems due to either M-CSF produced in situ or expression of receptor for M-CSF. Macrophages present in tissues of the mutant mice were immature and appear to be regulated by either granulocyte/macrophage colony-stimulating factor and/or interleukin-3 produced in situ or receptor expression. Northern blot analysis revealed different expressions of GM-CSF and IL-3 mRNA in various tissues of the op/op mice. However, granulocyte/macrophage colony-stimulating factor and interleukin-3 in serum were not detected by enzyme-linked immunosorbent assay. The immature macrophages differentiated and matured into resident macrophages after M-CSF administration, and some of these cells proliferated in response to M-CSF.

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  • Marks SC, Jr, Lane PW. Osteopetrosis, a new recessive skeletal mutation on chromosome 12 of the mouse. J Hered. 1976 Jan-Feb;67(1):11–18. [PubMed]
  • Marks SC., Jr Morphological evidence of reduced bone resorption in osteopetrotic (op) mice. Am J Anat. 1982 Feb;163(2):157–167. [PubMed]
  • Marks SC, Jr, Seifert MF, McGuire JL. Congenitally osteopetrotic (oplop) mice are not cured by transplants of spleen or bone marrow cells from normal littermates. Metab Bone Dis Relat Res. 1984;5(4):183–186. [PubMed]
  • Wiktor-Jedrzejczak WW, Ahmed A, Szczylik C, Skelly RR. Hematological characterization of congenital osteopetrosis in op/op mouse. Possible mechanism for abnormal macrophage differentiation. J Exp Med. 1982 Nov 1;156(5):1516–1527. [PMC free article] [PubMed]
  • Wiktor-Jedrzejczak W, Urbanowska E, Aukerman SL, Pollard JW, Stanley ER, Ralph P, Ansari AA, Sell KW, Szperl M. Correction by CSF-1 of defects in the osteopetrotic op/op mouse suggests local, developmental, and humoral requirements for this growth factor. Exp Hematol. 1991 Nov;19(10):1049–1054. [PubMed]
  • Wiktor-Jedrzejczak W, Ratajczak MZ, Ptasznik A, Sell KW, Ahmed-Ansari A, Ostertag W. CSF-1 deficiency in the op/op mouse has differential effects on macrophage populations and differentiation stages. Exp Hematol. 1992 Sep;20(8):1004–1010. [PubMed]
  • Felix R, Cecchini MG, Fleisch H. Macrophage colony stimulating factor restores in vivo bone resorption in the op/op osteopetrotic mouse. Endocrinology. 1990 Nov;127(5):2592–2594. [PubMed]
  • Felix R, Cecchini MG, Hofstetter W, Elford PR, Stutzer A, Fleisch H. Impairment of macrophage colony-stimulating factor production and lack of resident bone marrow macrophages in the osteopetrotic op/op mouse. J Bone Miner Res. 1990 Jul;5(7):781–789. [PubMed]
  • Chambers TJ, Loutit JF. A functional assessment of macrophages from osteopetrotic mice. J Pathol. 1979 Oct;129(2):57–63. [PubMed]
  • Naito M, Hayashi S, Yoshida H, Nishikawa S, Shultz LD, Takahashi K. Abnormal differentiation of tissue macrophage populations in 'osteopetrosis' (op) mice defective in the production of macrophage colony-stimulating factor. Am J Pathol. 1991 Sep;139(3):657–667. [PMC free article] [PubMed]
  • Umeda S, Takahashi K, Naito M, Shultz LD, Takagi K. Neonatal changes of osteoclasts in osteopetrosis (op/op) mice defective in production of functional macrophage colony-stimulating factor (M-CSF) protein and effects of M-CSF on osteoclast development and differentiation. J Submicrosc Cytol Pathol. 1996 Jan;28(1):13–26. [PubMed]
  • Metcalf D. The molecular biology and functions of the granulocyte-macrophage colony-stimulating factors. Blood. 1986 Feb;67(2):257–267. [PubMed]
  • Wiktor-Jedrzejczak W, Urbanowska E, Szperl M. Granulocyte-macrophage colony-stimulating factor corrects macrophage deficiencies, but not osteopetrosis, in the colony-stimulating factor-1-deficient op/op mouse. Endocrinology. 1994 Apr;134(4):1932–1935. [PubMed]
  • Kodama H, Yamasaki A, Nose M, Niida S, Ohgame Y, Abe M, Kumegawa M, Suda T. Congenital osteoclast deficiency in osteopetrotic (op/op) mice is cured by injections of macrophage colony-stimulating factor. J Exp Med. 1991 Jan 1;173(1):269–272. [PMC free article] [PubMed]
  • Usuda H, Naito M, Umeda S, Takahashi K, Shultz LD. Ultrastructure of macrophages and dendritic cells in osteopetrosis (op) mutant mice lacking macrophage colony-stimulating factor (M-CSF/CSF-1) activity. J Submicrosc Cytol Pathol. 1994 Jan;26(1):111–119. [PubMed]
  • Kodama H, Yamasaki A, Abe M, Niida S, Hakeda Y, Kawashima H. Transient recruitment of osteoclasts and expression of their function in osteopetrotic (op/op) mice by a single injection of macrophage colony-stimulating factor. J Bone Miner Res. 1993 Jan;8(1):45–50. [PubMed]
  • Cecchini MG, Dominguez MG, Mocci S, Wetterwald A, Felix R, Fleisch H, Chisholm O, Hofstetter W, Pollard JW, Stanley ER. Role of colony stimulating factor-1 in the establishment and regulation of tissue macrophages during postnatal development of the mouse. Development. 1994 Jun;120(6):1357–1372. [PubMed]
  • Takahashi K, Naito M, Umeda S, Shultz LD. The role of macrophage colony-stimulating factor in hepatic glucan-induced granuloma formation in the osteopetrosis mutant mouse defective in the production of macrophage colony-stimulating factor. Am J Pathol. 1994 Jun;144(6):1381–1392. [PMC free article] [PubMed]
  • Honda Y, Takahashi K, Naito M, Fujiyama S. The role of macrophage colony-stimulating factor in the differentiation and proliferation of Kupffer cells in the liver of protein-deprived mice. Lab Invest. 1995 Jun;72(6):696–706. [PubMed]
  • Hume DA, Robinson AP, MacPherson GG, Gordon S. The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80. Relationship between macrophages, Langerhans cells, reticular cells, and dendritic cells in lymphoid and hematopoietic organs. J Exp Med. 1983 Nov 1;158(5):1522–1536. [PMC free article] [PubMed]
  • Hume DA, Loutit JF, Gordon S. 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. 1984 Mar;66:189–194. [PubMed]
  • Leenen PJ, de Bruijn MF, Voerman JS, Campbell PA, van Ewijk W. Markers of mouse macrophage development detected by monoclonal antibodies. J Immunol Methods. 1994 Sep 14;174(1-2):5–19. [PubMed]
  • Malorny U, Michels E, Sorg C. A monoclonal antibody against an antigen present on mouse macrophages and absent from monocytes. Cell Tissue Res. 1986;243(2):421–428. [PubMed]
  • Kraal G, Janse M. Marginal metallophilic cells of the mouse spleen identified by a monoclonal antibody. Immunology. 1986 Aug;58(4):665–669. [PMC free article] [PubMed]
  • Cammer W, Sacchi R, Sapirstein V. Immunocytochemical localization of carbonic anhydrase in the spinal cords of normal and mutant (shiverer) adult mice with comparisons among fixation methods. J Histochem Cytochem. 1985 Jan;33(1):45–54. [PubMed]
  • Dijkstra CD, Van Vliet E, Döpp EA, van der Lelij AA, Kraal G. Marginal zone macrophages identified by a monoclonal antibody: characterization of immuno- and enzyme-histochemical properties and functional capacities. Immunology. 1985 May;55(1):23–30. [PMC free article] [PubMed]
  • Leenen PJ, Melis M, Slieker WA, Van Ewijk W. Murine macrophage precursor characterization. II. Monoclonal antibodies against macrophage precursor antigens. Eur J Immunol. 1990 Jan;20(1):27–34. [PubMed]
  • McCormack JM, Leenen PJ, Walker WS. Macrophage progenitors from mouse bone marrow and spleen differ in their expression of the Ly-6C differentiation antigen. J Immunol. 1993 Dec 1;151(11):6389–6398. [PubMed]
  • de Bruijn MF, Slieker WA, van der Loo JC, Voerman JS, van Ewijk W, Leenen PJ. Distinct mouse bone marrow macrophage precursors identified by differential expression of ER-MP12 and ER-MP20 antigens. Eur J Immunol. 1994 Oct;24(10):2279–2284. [PubMed]
  • van der Loo JC, Slieker WA, Kieboom D, Ploemacher RE. Identification of hematopoietic stem cell subsets on the basis of their primitiveness using antibody ER-MP12. Blood. 1995 Feb 15;85(4):952–962. [PubMed]
  • Tominaga A, Mita S, Kikuchi Y, Hitoshi Y, Takatsu K, Nishikawa S, Ogawa M. Establishment of IL-5-dependent early B cell lines by long-term bone marrow cultures. Growth Factors. 1989;1(2):135–146. [PubMed]
  • Oghiso Y, Yamada Y, Ando K, Ishihara H, Shibata Y. Differential induction of prostaglandin E2-dependent and -independent immune suppressor cells by tumor-derived GM-CSF and M-CSF. J Leukoc Biol. 1993 Jan;53(1):86–92. [PubMed]
  • Lee JC, Hapel AJ, Ihle JN. Constitutive production of a unique lymphokine (IL 3) by the WEHI-3 cell line. J Immunol. 1982 Jun;128(6):2393–2398. [PubMed]
  • Stanley ER, Guilbert LJ, Tushinski RJ, Bartelmez SH. CSF-1--a mononuclear phagocyte lineage-specific hemopoietic growth factor. J Cell Biochem. 1983;21(2):151–159. [PubMed]
  • Wijffels JF, de Rover Z, Kraal G, Beelen RH. Macrophage phenotype regulation by colony-stimulating factors at bone marrow level. J Leukoc Biol. 1993 Mar;53(3):249–255. [PubMed]
  • Morioka Y, Naito M, Sato T, Takahashi K. Immunophenotypic and ultrastructural heterogeneity of macrophage differentiation in bone marrow and fetal hematopoiesis of mouse in vitro and in vivo. J Leukoc Biol. 1994 May;55(5):642–651. [PubMed]
  • Takahashi K, Umeda S, Shultz LD, Hayashi S, Nishikawa S. Effects of macrophage colony-stimulating factor (M-CSF) on the development, differentiation, and maturation of marginal metallophilic macrophages and marginal zone macrophages in the spleen of osteopetrosis (op) mutant mice lacking functional M-CSF activity. J Leukoc Biol. 1994 May;55(5):581–588. [PubMed]
  • van Rooijen N, Kors N, Kraal G. Macrophage subset repopulation in the spleen: differential kinetics after liposome-mediated elimination. J Leukoc Biol. 1989 Feb;45(2):97–104. [PubMed]
  • SNOOK T. STUDIES ON THE PERIFOLLICULAR REGION OF THE RAT'S SPLEEN. Anat Rec. 1964 Feb;148:149–159. [PubMed]
  • Elomaa O, Kangas M, Sahlberg C, Tuukkanen J, Sormunen R, Liakka A, Thesleff I, Kraal G, Tryggvason K. Cloning of a novel bacteria-binding receptor structurally related to scavenger receptors and expressed in a subset of macrophages. Cell. 1995 Feb 24;80(4):603–609. [PubMed]
  • Kraal G, Janse M, Claassen E. Marginal metallophilic macrophages in the mouse spleen: effects of neonatal injections of MOMA-1 antibody on the humoral immune response. Immunol Lett. 1988 Feb;17(2):139–144. [PubMed]
  • Kraal G, Ter Hart H, Meelhuizen C, Venneker G, Claassen E. Marginal zone macrophages and their role in the immune response against T-independent type 2 antigens: modulation of the cells with specific antibody. Eur J Immunol. 1989 Apr;19(4):675–680. [PubMed]
  • Humphrey JH. Tolerogenic or immunogenic activity of hapten-conjugated polysaccharides correlated with cellular localization. Eur J Immunol. 1981 Mar;11(3):212–220. [PubMed]
  • Claassen E, Ott A, Boersma WJ, Deen C, Schellekens MM, Dijkstra CD, Kors N, Van Rooijen N. Marginal zone of the murine spleen in autotransplants: functional and histological observations in the response against a thymus-independent type 2 antigen. Clin Exp Immunol. 1989 Sep;77(3):445–451. [PMC free article] [PubMed]
  • Akagawa KS, Kamoshita K, Tokunaga T. Effects of granulocyte-macrophage colony-stimulating factor and colony-stimulating factor-1 on the proliferation and differentiation of murine alveolar macrophages. J Immunol. 1988 Nov 15;141(10):3383–3390. [PubMed]
  • Nakata K, Akagawa KS, Fukayama M, Hayashi Y, Kadokura M, Tokunaga T. Granulocyte-macrophage colony-stimulating factor promotes the proliferation of human alveolar macrophages in vitro. J Immunol. 1991 Aug 15;147(4):1266–1272. [PubMed]
  • Stanley E, Lieschke GJ, Grail D, Metcalf D, Hodgson G, Gall JA, Maher DW, Cebon J, Sinickas V, Dunn AR. Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5592–5596. [PMC free article] [PubMed]
  • Nishinakamura R, Nakayama N, Hirabayashi Y, Inoue T, Aud D, McNeil T, Azuma S, Yoshida S, Toyoda Y, Arai K, et al. Mice deficient for the IL-3/GM-CSF/IL-5 beta c receptor exhibit lung pathology and impaired immune response, while beta IL3 receptor-deficient mice are normal. Immunity. 1995 Mar;2(3):211–222. [PubMed]
  • Emerson SG, Yang YC, Clark SC, Long MW. Human recombinant granulocyte-macrophage colony stimulating factor and interleukin 3 have overlapping but distinct hematopoietic activities. J Clin Invest. 1988 Oct;82(4):1282–1287. [PMC free article] [PubMed]
  • Sonoda Y, Yang YC, Wong GG, Clark SC, Ogawa M. Analysis in serum-free culture of the targets of recombinant human hemopoietic growth factors: interleukin 3 and granulocyte/macrophage-colony-stimulating factor are specific for early developmental stages. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4360–4364. [PMC free article] [PubMed]
  • Bagley CJ, Woodcock JM, Hercus TR, Shannon MF, Lopez AF. Interaction of GM-CSF and IL-3 with the common beta-chain of their receptors. J Leukoc Biol. 1995 May;57(5):739–746. [PubMed]

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