Erythropoiesis and Macrophage Subsets in Medullary and Extramedullary Sites

  • J. P. de Jong
  • P. G. J. Nikkels
  • A. H. Piersma
  • R. E. Ploemacher
Conference paper
Part of the NATO ASI Series book series (volume 8)


Morphological and functional evidence exists that macrophages support in vivo erythropoiesis. Using in vitro cultured primary adherent cells from murine bone marrow as antigenic source, we have prepared a hybridoma cell line secreting a monoclonal antibody (mAb) to reticular cells of bone marrow and non-lymphoid domains in the spleen. The mAb (α-ER-HR3) also binds to some elongated cells in the subcutaneous tissue and to intertubular areas of the renal medulla. In addition, the ER-HR3 antigen is expressed on some reticular cells in the capsular sinuses and paracortex of lymph nodes and in the lamina propria of the ilium and colon, with increasing expression towards the distal ileum. The expression of the ER-HR3 antigen in non-lymphoid domains of hemopoietic organs is proposed to be associated with adult type hemoglobin (Hb) erythropoiesis as evidenced by (1) the absence in the yolk sac, (2) the exact correlation with the presence of adult type Hb erythropoiesis, but not granulopoiesis, in fetal and neonatal liver and spleen and postnatal bone marrow and spleen, and (3) the correlation with phenylhydrazine-induced hepatic erythropoiesis in the adult liver.

Following injection of highly purified -ER-HR3 into neonatal mice, a transient decrease of hemopoietic progenitor cells, but not of day-7 and day-12 CFU-S, was observed in the bone marrow,resulting in a moderate macrocytic anemia. Injection of -ER-HR3 also limited the erythropoietin-induced 59Fe incorporation in the bone marrow of adult hypertransfused mice. The data obtained so far strongly suggest that the ER-HR3 antigen is exclusively expressed by a macrophage subset.


Bone Marrow Murine Bone Marrow Hemopoietic Stem Cell Macrophage Subset Fibroblast Coloni 
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.


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  1. 1.
    Bessis MC and Breton-Gorius J (1962). Iron metabolism in the bone marrow as seen by electron microscopy: a critical review. Blood 19: 635–663.PubMedGoogle Scholar
  2. 2.
    Orlic D, Gordon AD and Rhodin JA (1965). An ultrastructural study of erythropoietin-induced red cell formation in mouse spleen. J Ultrastruct Res 13: 516–542.PubMedCrossRefGoogle Scholar
  3. 3.
    Sorenson Dg (1961). An electronmicroscopic study of hematopoiesis in the yolk sac. Lab Invest 10: 178–183.Google Scholar
  4. 4.
    Zamboni L (1965). Electronmicroscopic studies of blood em- bryogenesis in human. I. The ultrastructure of the fetal liver. J Ultrastruct Res 12: 509–514.PubMedCrossRefGoogle Scholar
  5. 5.
    Naito M and Wisse E (1977). Observation on the fine structure and cytochemistry of sinusoidal cells in fetal and neonatal rat liver. In: Wisse E and Knook KD (eds) Kupffer Cells and Other Liver Sinusoidal Cells. Elsevier. pp. 497–506.Google Scholar
  6. 6.
    Le Charpentier Y and Prenant M (1975). Isolement de l’ilot erythroblastique. Etude en microscope optique et electronique a balayage. Nouvell Revue Francaise d’Hematologie 15: 119–140.Google Scholar
  7. 7.
    Macario AJ, Dugan C, Perz-Lloret IL and Conweay de Macario E (1981). Purification of erythroblastic nests. Blood 57: 922–927.PubMedGoogle Scholar
  8. 8.
    Crocker PR and Gordon S (1985). Isolation and characteriz- ation of resident stromal macrophages and hematopoietic cell clusters from mouse bone marrow. J Exp Med 162: 993–1011.PubMedCrossRefGoogle Scholar
  9. 9.
    Ploemacher RE and van Soest PL (1977). Morphological investigations on phenylhydrazine-induced erythropoiesis in the adult mouse liver. J Cell Tissue Res 178: 435–461.Google Scholar
  10. 10.
    Ben-Ishay Z and Yoffey JM (1974). Ultrastructural studies of erythroblastic islands of rat bone marrow. III. Effects of sublethal irradiation. Lab Invest 30: 320–332.PubMedGoogle Scholar
  11. 11.
    Ploemacher RE, van Soest PL, Wagemaker G and van’t Hull E (1979). Particle-induced erythropoietin-independent effects on erythroid precursor cells in murine bone marrow. Cell Tissue Kinet 12: 539–550.PubMedGoogle Scholar
  12. 12.
    Allen TD and Dexter TM (1982). Ultrastructural aspects of erythropoietic differentiation in long-term bone marrow culture. Differentiation 21: 86–94.PubMedCrossRefGoogle Scholar
  13. 13.
    Cavallin-Stahl F, Berg B and Brandt L (1974). Reticulum cells and erythroblasts in the bone marrow of anaemic patients. Acta Med Scand 195: 185–189.PubMedCrossRefGoogle Scholar
  14. 14.
    Shortman K, Diener E, Russel P and Armstrong WD (1970). The role of nonlymphoid accessory cells in the immune response to different antigens. J Exp Med 131: 461–482.PubMedCrossRefGoogle Scholar
  15. 15.
    Rosenstreich DL, Farrar JJ and Dougherty S (1976). Absolute macrophage dependendeny of T lymphocyte activation by mitogens. J Immunol 116: 131–139.PubMedGoogle Scholar
  16. 16.
    Rich IN, Heit W and Kubanek B (1982). Extrarenal erythropoietin production by macrophages. Blood 60: 1007–1018.PubMedGoogle Scholar
  17. 17.
    Rich IN (1986). A role for the macrophage in normal hemopoiesis. I. Functional capacity of bone marrow-derived macrophages to release hemopoietic growth factors. Exp Hematol 14: 738–745.PubMedGoogle Scholar
  18. 18.
    Rich IN (1986). A role for the macrophage in normal hemopoiesis. II. Effect of varying physiological oxygen tensions on the release of hemopoietic growth factors from bone marrow-derived macrophages in vitro. Exp Hematol 14: 746–751.PubMedGoogle Scholar
  19. 19.
    Wright EG, Riches AC and Lord BI (1982). Stimulation of hemopoietic stem cell proliferation: characteristics of the stimulator-producing cells. Leuk Res 6: 531–539.PubMedCrossRefGoogle Scholar
  20. 20.
    Till JE and McCulloch EA (1961). A direct measurement of the radiation sensitivity of normal bone marrow cells. Rad Res 14: 213–222.CrossRefGoogle Scholar
  21. 21.
    DeJong JP, Nikkels PGJ, Brockbank KGM, Ploemacher RE and Voerman JSE (1985). Comparative in vitro effects of cyclophosphamide derivatives on murine bone marrow-derived stromal and hemopoietic progenitor cell classes. Cancer Res 45: 4001–4005.Google Scholar
  22. 22.
    Ploemacher RE and van Soest PL (1977). Morphological investigations on ectopic erythropoiesis in experimental hemolytic anemia. Cytobiologie 15: 391–409.Google Scholar
  23. 23.
    Kearny JF, Radbruch A, Liesegang B and Rajewsky K (1979). A new mouse myeloma cell line that has lost immunological expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol 123: 1548–1550.Google Scholar
  24. 24.
    Piersma AH, Ploemacher RE, Brockbank KGM and Ottenheim CPE (1985). Monoclonal antibodies identify specific determinants on reticular cells in murine embryonic and adult hemopoietic stroma. In: Baum SJ, Pluznik DJ, Rozenszajn LA (eds) Experimental Hematology Today, Springer Verlag, pp. 50–54.Google Scholar
  25. 25.
    DeJong JP, Nikkels PGJ, Voerman JSA, Willemse R and Ploemacher RE. A monoclonal antibody (-ER-HR3) recognising a subpopulation of murine macrophages. (Submitted for publication).Google Scholar
  26. 26.
    Hume DA, Loutit JF and Gordon S (1984). The mononuclear phagocyte system of the mouse defined by immunohistochemical localisation of antigen F4/80: macrophages of the bone and associated connective tissue. J Cell Sci 66, 189–194.PubMedGoogle Scholar
  27. 27.
    Springer T, Galfre G, Secher DS, Milstein C (1979). Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur J Immunol 9: 301–306.PubMedCrossRefGoogle Scholar
  28. 28.
    Ho M-K and Springer TA (1982). Mac-2, a novel 32,000 Mr mouse macrophage subpopulation-specific antigen defined by monoclonal antibodies. J Immunol 128: 1221–1228.PubMedGoogle Scholar
  29. 29.
    Ho M-K and Springer TA (1983). Tissue distribution, structural characterization and biosynthesis of Mac-3, a macrophage surface glycoprotein exhibiting molecular weight heterogeneity. J Biol Chem 258: 636–642.PubMedGoogle Scholar
  30. 30.
    Austyn JM and Gordon S (1981). A monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol 11: 805–815.PubMedCrossRefGoogle Scholar
  31. 31.
    Koren HS, Handwerger BS and Wunderlich JR (1975). Identification of macrophage-like characteristics in a cultured murine tumor line. J Immunol 114: 894–897.PubMedGoogle Scholar
  32. 32.
    Ralph P, Prichard J and Cohn M (1975). Reticulum cell sarcoma: an effector cell in antobody-dependent cell-mediated immunity. J Immunol 114: 898–905.PubMedGoogle Scholar
  33. 33.
    Ralph P, Nakoinz I and Raschke WC (1974). Lymphosarcoma cell growth is selectively inhibited by B lymphocyte mitogens: LPS, dextran sulphate and PPD. Biochem Biophys Res Commun 61: 1268–1275.PubMedCrossRefGoogle Scholar
  34. 34.
    Warner NL, Moore MA and Metcalf D (1969). A transplantable myelomonocytic leukemia in BALB/c mice: cytology, karyotype and muramidase content. J Natl Can c Inst 43: 963977.Google Scholar
  35. 35.
    Friedenstein AJK, Chailakhyan RK and Lalykinc KS (1970). The development of fibroblast colonies in monolayer cultures of guinea pig bone marrow and spleen cells. Cell Tissue Kinet 3: 393–403.PubMedGoogle Scholar
  36. 36.
    Wilson FD, O’grady L, McNeill CJ and Munn SL (1974). The formation of bone marrow derived fibroblastic plaques in vitro: preliminary results contrasting these populations to CFU-C. Exp Hematol 2: 343–354.PubMedGoogle Scholar
  37. 37.
    Brockbank KGM, Piersma AH, Ploemacher RE and Voerman JSA (1985). Colony-stimulating activity production by hemopoietic organ fibroblastoid cells in vitro. Acta Haemat 69: 369–375.CrossRefGoogle Scholar
  38. 38.
    Brockbank KGM, Piersma AH, Ploemacher RE and Voerman JSA (1985). Stromal cells ( CFU-F) in normal and genetically anemic mouse strains. Acta Haemat 74: 75–80.PubMedCrossRefGoogle Scholar
  39. 39.
    Piersma AH, Brockbank KGM and Ploemacher RE (1984). Regulation of in vitro myelopoiesis by a hemopoietic stromal fibroblastic cell line. Exp Hematol 12: 617–623.PubMedGoogle Scholar
  40. 40.
    Petrakis NL, Pons S and Lee RE (1969). An experimental analysis of factors affecting the localization of embryonic bone marrow. In: Farnes P (ed) Hemic Cell In Vitro. Williams and Wilkins.Google Scholar
  41. 41.
    Metcalf D and Moore MAS (1971). Haemopoietic cells. North Holland Publishing Company, Amsterdam.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • J. P. de Jong
    • 1
  • P. G. J. Nikkels
    • 1
  • A. H. Piersma
    • 1
  • R. E. Ploemacher
    • 1
  1. 1.Department of Cell Biology and GeneticsErasmus UniversityRotterdamThe Netherlands

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