Skip to main content
SpringerLink
Log in

Functional Heterogeneity of Colony-Stimulating Factor-Induced Human Nonocyte-Derived Macrophages

  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Macrophages have various functions and play a critical role in host defense and the maintenance of homeostasis. However, macrophages are heterogeneous and exhibit a wide range of phenotypes with regard to their morphology, cell surface antigen expression, and function. When blood monocytes are cultured in medium alone in vitro, monocytes die, and colony-stimulating factors (CSFs) such as macrophage (M)-CSF or granulocyte-macrophage (GM)-CSF are necessary for their survival and differentiation into macrophages. However, M-CSF-induced monocyte-derived macrophages (M-MΦ) and GM-CSF-induced monocyte-derived macrophages (GM-MΦ) are distinct in their morphology, cell surface antigen expression, and functions, including Fcγ receptor mediated-phagocytosis, H2O2 production, H2O2 sensitivity, catalase activity, susceptibility to human immunodeficiency virus type 1 andMycobacterium tuberculosis, and suppressor activity. The characteristics of GM-MΦ resemble those of human alveolar macrophages.

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

  1. Kennedy DW, Abkowitz JL. Mature monocytic cells enter tissues and engraft.Proc Natl Acad Sci U S A. 1998;95:14944–14949.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Hume DA, Robinson AP, MacPherson GG, Gordon S. The mononuclear phagocyte system of the mouse defined by immuno- histochemical localization of antigen F4/80: relationship between macrophages, Langerhans cells, reticular cells, and dendritic cells in lymphoid and hematopoietic organs.J Exp Med. 1983;158: 1522–1536.

    Article  PubMed  CAS  Google Scholar 

  3. Burdach S, Nishinakamura R, Dirksen U, et al. The physiologic role of interleukin-3, interleukin-5, granulocyte-macrophage colony- stimulating factor, and the beta c receptor system.Curr Opin Hematol. 1998;5:177–180.

    Article  PubMed  CAS  Google Scholar 

  4. Motoyoshi K. Biological activities and clinical application of M-CSF.Int J Hematol. 1998;67:109–122.

    Article  PubMed  CAS  Google Scholar 

  5. Motoyoshi, K. Macrophage colony-stimulating factor.Nippon Rinsho. 1999;57(suppl):765–768.

    PubMed  Google Scholar 

  6. Akagawa KS, Kamoshita K, Tokunaga T. Effects of granulocyte- macrophage colony-stimulating factor and colony-stimulating fac- tor-1 on the proliferation and differentiation of murine alveolar macrophages.J Immunol. 1988;141:3383–3390.

    PubMed  CAS  Google Scholar 

  7. Burgess W, Camakaris J, Metcalf D, et al. Purification and properties of colony-stimulating factor from mouse lung-conditioned medium.J Biol Chem. 1997;252:1998–2003.

    Google Scholar 

  8. Dranoff G, Crawford AD, Sadelain M, et al. Involvement of granu- locyte-macrophage colony-stimulating factor in pulmonary home- ostasis.Science. 1994;264:713–716.

    Article  PubMed  CAS  Google Scholar 

  9. Robb L, Drinkwater CC, Metcalf.D, et al. Hematopoietic and lung abnormalities in mice with a null mutation of the common beta subunit of the receptors for granulocyte-macrophage colony-stimulating factor and interleukins 3 and 5.Proc Natl Acad Sci U S A. 1995;92:9565–9569.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Zsengeller ZK, Reed JA, Bachurski CJ, et al. Adenovirus-mediated granulocyte-macrophage colony-stimulating factor improves lung pathology of pulmonary alveolar proteinosis in granulocyte- macrophage colony-stimulating factor-deficient mice.Hum Gene Ther. 1998;9:2101–2109.

    Article  PubMed  CAS  Google Scholar 

  11. Naito M, Umeda S, Takahashi K, et al. Macrophage differentiation and granulomatous inflammation in osteopetrotic mice (op/op) defective in the production of CSF-1.Mol Reprod Dev. 1997: 46:85–91.

    Article  PubMed  CAS  Google Scholar 

  12. Akagawa KS,Takasuka N, Nozaki Y, et al. Generation of CD1+RelB+ dendritic cells and tartrate-resistant acid phosphatase-positive osteoclast-like multinucleated giant cells from human monocytes.Blood. 1996;88:4029–4039.

    PubMed  CAS  Google Scholar 

  13. Akagawa K. Differentiation and function of human monocytes.Hum Cell. 1994;7:116–120.

    PubMed  CAS  Google Scholar 

  14. Akagawa KS. Generation of two phenotypically distinct types of macrophages, CD1+ dendritic cells, TRAP+ osteoclast-like multinucleated giant cells from human monocytes.Jpn J Med Mycol. 1997;38:209–214.

    Article  CAS  Google Scholar 

  15. Koyama Y,Yamanoha B, Yoshida T, et al. A novel monoclonal antibody induces the differentiation of monocyte leukemic cells.Biochem Biophys Res Commun. 1990;168:898–904.

    Article  PubMed  CAS  Google Scholar 

  16. Young DA, Lowe LD, Clark SC. Comparison of the effects of IL-3, granulocyte-macrophage colony-stimulating factor, and macrophage colony-stimulating factor in supporting monocyte differentiation in culture: analysis of macrophage antibody-dependent cellular cytotoxicity.J Immunol. 1990;145:607–615.

    PubMed  CAS  Google Scholar 

  17. De Nichilo MO, Burns GF, Koyama Y, et al. Granulocyte-macrophage and macrophage colony-stimulating factors differentially regulate alpha v integrin expression on cultured human macrophages.Proc Natl Acad Sci U S A. 1993;90:2517–2521.

    Article  Google Scholar 

  18. Nakata K,Akagawa KS, Fukayama M, et al. Granulocyte-macrophage colony-stimulating factor promotes the proliferation of human alveolar macrophages in vitro.J Immunol. 1991;147:1266–1272.

    PubMed  CAS  Google Scholar 

  19. Radzun HJ, Kreipe H, Heidorn K, Parwaresch MR. Modulation of c-fms proto-oncogene expression in human blood monocytes and macrophages.J Leukoc Biol. 1988;44:198–204.

    Article  PubMed  CAS  Google Scholar 

  20. Andreesen R, Brugger W, Scheibenbogen.C, et al. Surface phenotype analysis of human monocyte to macrophage maturation.J Leukoc Biol. 1990;47:490–497.

    Article  PubMed  CAS  Google Scholar 

  21. Krombach F, Gerlach JT, Padovan.C, et al. Characterization and quantification of alveolar monocyte-like cells in human chronic inflammatory lung disease.Eur Respir J. 1996;9:984–991.

    Article  PubMed  CAS  Google Scholar 

  22. Crowley MT, Costello PS, Fitzer-Attas.CJ, et al. A critical role for Syk in signal transduction and phagocytosis mediated by Fcgamma receptors on macrophages.J Exp Med. 1997;186:1027–1039.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Kiefer F, Brumell J, Al-Alawi N, et al. The Syk protein tyrosine kinase is essential for Fcgamma receptor signaling in macrophages and neutrophils.Mol Cell Biol. 1998;18:4209–4220.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Fitzer-Attas, CJ, Lowry M, Crowley MT, et al. Fcgamma receptor- mediated phagocytosis in macrophages lacking the Src family tyro- sine kinases Hck, Fgr, and Lyn.J Exp Med. 2000;191:669–682.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Ravetch JV, Bolland S. IgG Fc receptors.Annu Rev Immunol. 2001: 19:275–290.

    Article  PubMed  CAS  Google Scholar 

  26. Brooks D, Ravetch JV. Fc receptor signaling.Adv Exp Med Biol. 1994;365:185–195.

    Article  PubMed  CAS  Google Scholar 

  27. Komuro I, Keicho N, Iwamoto A, Akagawa KS. Human alveolar macrophages and granulocyte-macrophage colony-stimulating factor -induced monocyte-derived macrophages are resistant to H2O2 via their high basal and inducible levels of catalase activity.J Biol Chem. 2001;276:24360–24364.

    Article  PubMed  CAS  Google Scholar 

  28. Desai G, Nassar F, Brummer E, Stevens DA. Killing of Histoplasma capsulatum by macrophage colony stimulating factortreated human monocyte-derived macrophages: role for reactive oxygen intermediates.J Med Microbiol. 1995;43:224–229.

    Article  PubMed  CAS  Google Scholar 

  29. Nassar F, Brummer E, Stevens DA. Macrophage colony-stimulating factor (M-CSF) induction of enhanced anticryptococcal activity in human monocyte-derived macrophages: synergy with fluconazole for killing.Cell Immunol. 1995;164:113–118.

    Article  PubMed  CAS  Google Scholar 

  30. Danel C, Erzuru SC, Prayssac.P, et al. Gene therapy for oxidant injury-related diseases: adenovirus-mediated transfer of superoxide dismutase and catalase cDNAs protects against hyperoxia but not against ischemia-reperfusion lung injury.Hum Gene Ther. 1998;9:1487–1496.

    Article  PubMed  CAS  Google Scholar 

  31. Nakata K, Gotoh H, Watanabe J, et al. Augmented proliferation of human alveolar macrophages after allogeneic bone marrow transplantation.Blood. 1999;93:667–673.

    PubMed  CAS  Google Scholar 

  32. Forman HJ, Torres M. Redox signaling in macrophages.Mol Aspects Med. 2001;22:189–216.

    Article  PubMed  CAS  Google Scholar 

  33. Ghorpade A, Xia MQ, Hyman BT, et al. Role of the betachemokine receptors CCR3 and CCR5 in human immunodeficiency virus type 1 infection of monocytes and microglia.J Virol. 1998;72:3351–3361.

    PubMed  PubMed Central  CAS  Google Scholar 

  34. Lane BR, Markovitz DM, Woodford NL, et al. TNF-alpha inhibits HIV-1 replication in peripheral blood monocytes and alveolar macrophages by inducing the production of RANTES and decreasing C-C chemokine receptor 5 (CCR5) expression.J Immunol. 1999;163:3653–3661.

    PubMed  CAS  Google Scholar 

  35. Crowe SM, Sonza S. HIV-1 can be recovered from a variety of cells including peripheral blood monocytes of patients receiving highly active antiretroviral therapy: a further obstacle to eradication.J Leukoc Biol. 2000;68:345–350.

    PubMed  CAS  Google Scholar 

  36. Chun TW, Carruth L, Finzi D, et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection.Nature. 1997;387:183–188.

    Article  PubMed  CAS  Google Scholar 

  37. Li S, Juarez J, Alali M, et al. Persistent CCR5 utilization and enhanced macrophage tropism by primary blood human immunodeficiency virus type 1 isolates from advanced stages of disease and comparison to tissue-derived isolates.J Virol. 1999;73: 9741–9755.

    PubMed  PubMed Central  CAS  Google Scholar 

  38. Matsuda S, Akagawa K, Honda M, et al. Suppression of HIV replication in human monocyte-derived macrophages induced by granulocyte/macrophage colony-stimulating factor.AIDS Res Hum Retroviruses. 1995;11:1031–1038.

    Article  PubMed  CAS  Google Scholar 

  39. Berkowitz RD, Alexander S, Bare C, et al. CCR5- and CXCR4- utilizing strains of human immunodeficiency virus type 1 exhibit differential tropism and pathogenesis in vivo.J Virol. 1998;72: 10108–10117.

    PubMed  PubMed Central  CAS  Google Scholar 

  40. Lee B, Sharron M, Montaner LJ, et al. Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages.Proc Natl Acad Sci U S A. 1999;96:5215–5220.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Worgall S, Connor R, Kaner RJ, et al. Expression and use of human immunodeficiency virus type 1 coreceptors by human alveolar macrophages.J Virol. 1999;73:5865–5874.

    PubMed  PubMed Central  CAS  Google Scholar 

  42. Henderson AJ, Calame KL. CCAAT/enhancer binding protein (C/ EBP) sites are required for HIV-1 replication in primary macrophages but not CD4(+) T cells.Proc Natl Acad Sci U S A. 1997;94: 8714–8719.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Baer M, Williams SC, Dillner A, et al. Autocrine signals control CCAAT/enhancer binding protein beta expression, localization, and activity in macrophages.Blood. 1998;92:4353–4365.

    PubMed  CAS  Google Scholar 

  44. Xiong W, Hsieh CC, Kurtz AJ, et al. Regulation of CCAAT/ enhancer-binding protein-beta isoform synthesis by alternative translational initiation at multiple AUG start sites.Nucleic Acids Res. 2001;29:3087–3098.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Honda Y, Rogers L, Nakata K, et al. Type I interferon induces inhibitory 16-kD CCAAT/ enhancer binding protein (C/EBP)β, repressing the HIV-1 long terminal repeat in macrophages: pulmonary tuberculosis alters C/EBP expression, enhancing HIV-1 replication.J Exp Med. 1998;188:1255–1265.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Weiden M,Tanaka N, Qiao Y, et al. Differentiation of monocytes to macrophages switches the Mycobacterium tuberculosis effect on HIV-1 replication from stimulation to inhibition: modulation of interferon response and CCAAT/enhancer binding protein beta expression.J Immunol. 2000;165:2028–2039.

    Article  PubMed  CAS  Google Scholar 

  47. Moarefi I, LaFevre-Bernt M, Sicheri F, et al. Activation of the Srcfamily tyrosine kinase Hck by SH3 domain displacement.Nature. 1997;385:650–653.

    Article  PubMed  CAS  Google Scholar 

  48. Swingler S, Mann A, Jacque J, et al. HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages.Nat Med. 1999;5:997–1103.

    Article  PubMed  CAS  Google Scholar 

  49. Kurata S, Yamamoto N. Glucocorticoid can reduce the transcrip- tional activation of HIV-1 promoter through the reduction of active NF-kappaB.J Cell Biochem. 1999:76:13–19.

    Article  PubMed  CAS  Google Scholar 

  50. Klebanoff SJ, Headley CM. Activation of the human immunodeficiency virus-1 long terminal repeat by respiratory burst oxidants of neutrophils.Blood. 1999;93:350–356.

    PubMed  CAS  Google Scholar 

  51. Nakata K, Weiden M, Harkin T, Ho D, Rom WN. Low copy number and limited variability of proviral DNA in alveolar macrophages from HIV-1-infected patients: evidence for genetic differences in HIV-1 between lung and blood macrophage populations.Mol Med. 1995;1:744–757.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Russell DG. Mycobacterium tuberculosis: here today, and here tomorrow.Nat Rev Mol Cell Biol. 2001;2:569–577.

    Article  PubMed  CAS  Google Scholar 

  53. Deretic V, Fratti R. A. Mycobacterium tuberculosis phagosome.Mol Microbiol. 1999;31:1603–1609.

    Article  PubMed  CAS  Google Scholar 

  54. MacMicking JD, North RJ, LaCourse R, et al. Identification of nitric oxide synthase as a protective locus against tuberculosis.Proc Natl Acad Sci U S A. 1997;94:5243–5248.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Hanano R, Kaufmann SH. Nitric oxide production and mycobacterial growth inhibition by murine alveolar macrophages: the sequence of rIFN-gamma stimulation and Mycobacterium bovis BCG infection determines macrophage activation.Immunol Lett. 1995;45:23–27.

    Article  PubMed  CAS  Google Scholar 

  56. Rook GA, Taverne J, Leveton C, Steele, J. The role of gamma-interferon, vitamin D3 metabolites and tumour necrosis factor in the pathogenesis of tuberculosis.Immunology. 1987;62:229–234.

    PubMed  PubMed Central  CAS  Google Scholar 

  57. Akagawa KS, Komuro I, Yamazaki T, Haga S. Mechanisms of antibacterial activity of human macrophages against Mycobacterium tuberculosis. In: Proceedings of Thirty-sixth US-Japan Tuberculosis and Leprosy Research Conference; July 16, 2001; New Orleans, La.

  58. Gao PS, Fujishima S, Mao XQ, et al. Genetic variants of NRAMP1 and active tuberculosis in Japanese populations. International Tuberculosis Genetics Team.Clin Genet. 2000;58:74–76.

    Article  PubMed  CAS  Google Scholar 

  59. Bellamy R, Ruwende C, Corrah T, McAdam KP, Whittle HC, Hill AV.Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans.N Engl J Med. 1998;338:640–644.

    Article  PubMed  CAS  Google Scholar 

  60. Thoma-Uszynski S, Stenger S, Takeuchi O, et al. Induction of direct antimicrobial activity through mammalian toll-like receptors.Science. 2001;291:1544–1547.

    Article  PubMed  CAS  Google Scholar 

  61. Mochida-Nishimura K,Akagawa KS, Rich EA. Interleukin-10 contributes development of macrophage suppressor activities by macrophage colony-stimulating factor, but not by granulocytemacrophage colony-stimulating factor.Cell Immunol. 2001;214: 81–88.

    Article  PubMed  CAS  Google Scholar 

  62. Upham JW, Strickland DH, Robinson BW, Holt PG. Selective inhibition of T cell proliferation but not expression of effector function by human alveolar macrophages.Thorax. 1997;52:786–795.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Hashimoto S, Suzuki T, Dong HY, Yamazaki N, Matsushima, K. Serial analysis of gene expression in human monocytes and macrophages.Blood. 1999;94:837–844.

    PubMed  CAS  Google Scholar 

  64. Shibata Y, Berclaz PY, Chroneos ZC, et al. GM-CSF regulates alveolar macrophage differentiation and innate immunity in the lung through PU.1.Immunity. 2001;15:557–567.

    Article  PubMed  CAS  Google Scholar 

  65. Miyamoto T, Ohneda O, Arai F, et al. Bifurcation of osteoclasts and dendritic cells from common progenitors.Blood. 2001;98: 2544–2554.

    Article  PubMed  CAS  Google Scholar 

  66. Hashimoto S, Yamada M, Motoyoshi K, Akagawa KS. Enhancement of macrophage colony-stimulating factor-induced growth and differentiation of human monocytes by interleukin-10.Blood. 1997;89:315–321.

    PubMed  CAS  Google Scholar 

  67. Hashimoto S, Komuro I, Yamada, M, Akagawa KS. Il-10 inhibits granulocyte-macrophage colony-stimulating factor-dependent human monocyte survival at the early stage of the culture and inhibits the generation of macrophages.J Immunol. 2001;167: 3619–3625.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, 162-8640, Shinjuku-ku, Tokyo, Japan

    Kiyoko S. Akagawa

Authors
  1. Kiyoko S. Akagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kiyoko S. Akagawa.

About this article

Cite this article

Akagawa, K.S. Functional Heterogeneity of Colony-Stimulating Factor-Induced Human Nonocyte-Derived Macrophages. Int J Hematol 76, 27–34 (2002). https://doi.org/10.1007/BF02982715

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02982715

Key words

Search

Navigation