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Adhesion of Human Hematopoietic Progenitor Cells to Stromal Cells is Enhanced by Antibodies to CD44

  • Robert A. J. OostendorpEmail author
  • Elisabeth Spitzer
  • Peter Dörmer

Abstract

CD44 has been implicated to mediate adhesive interactions between hematopoietic progenitor cells and the stromal microenvironment. Ligands of CD44 include several extracellular matrix components, such as hyaluronic acid and fibronectin. Antibodies against CD44 have been shown to induce homotypic T-cell aggregation, and to stimulate T- and NK-cell activity. We hypothesized that CD44 could similarly amplify interactions of blast colony-forming cells and bone marrow stromal cells. Indeed, we have previously found that the anti-CD44 antibody NKI-P2 enhanced VLA-4 dependent interactions. Here, we studied an additional panel of 19 anti-CD44 antibodies from the 5th Workshop on Leukocyte Differentiation antigens, to find out whether amplification was associated with a particular CD44-epitope. None of these antibodies showed inhibitory activity, whereas nine significantly increased the number of blast colonies more than 2-fold. Seven of these recognized epitope 1, and two epitope 2. More than 4-fold enhancement was only observed with epitope 1 antibodies: 4.C3 (4.4-fold), 212.3 (6.3-fold), L178 (9.1-fold), and NIH44-1 (9.2-fold). Our data suggest that primarily epitope 1 is associated with enhancement of colony formation. Furthermore, the findings support the role of CD44 as an amplifier in progenitor-BMSC interactions.

Keywords

Hyaluronic Acid Bone Marrow Stromal Cell Stromal Microenvironment Adhesion Phase Human Hematopoietic Progenitor Cell 
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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References

  1. 1.
    . Gunji Y, Nakamura M, Hagiwara T, Hayakawa K, Matsushita H, Osawa H, Nagayoshi K, Nakauchi H, Yanagisawa M, Miura Y, Suda T: Expression and function of adhesion molecules on human hematopoietic stem cells: CD34+LFA-1- cells are more primitive than CD34+LFA-1- cells. Blood 80: 429, 1991Google Scholar
  2. 2.
    . Miyake K, Medina KL, Hayashi S-I, Ono S, Hamaoka T, Kincade PW: Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long-term bone marrow cultures. J Exp Med 171: 477, 1990PubMedCrossRefGoogle Scholar
  3. 3.
    . Verfaillie CM, Benis A, Iida J, McGlave PB, McCarthy JB: Adhesion of committed human hematopoietic progenitors to synthetic peptides from the C-terminal heparin-binding domain of fibronectin: cooperation between the integrin α4ßl and the CD44 adhesion receptor. Blood 84: 1802, 1994PubMedGoogle Scholar
  4. 4.
    . Koopman G, van Kooyk Y, de Graaff M, Meijer CJLM, Figdor CG, Pals ST: Triggering of the CD44 antigen on T-lymphocytes promotes T-cell adhesion through the LFA-1 pathway. J Immunol 145: 3589, 1990PubMedGoogle Scholar
  5. 5.
    . Belitsos PC, Hildreth JEK, August JT: Homotypic cell aggregation induced by anti-CD44(Pgp-l) monoclonal antibodies and related to CD44(Pgp-l) expression. J Immunol 144: 1661, 1991Google Scholar
  6. 6.
    . Tan PHS, Santos EB, Rossbach H-C, Sandmaier BM: Enhancement of natural killer activity by an antibody to CD44. J Immunol 150: 812, 1993PubMedGoogle Scholar
  7. 7.
    . Dittel BN, LeBien TW: Amplification of B cell precursor/bone marrow stromal cell adhesion with antibodies to CD44. Tissue Antigens 4: 271 (AS056), 1993Google Scholar
  8. 8.
    . Pals ST, Hogervorst F, Keizer GD, Thepen T, Horst E, Figdor CG: Identification of a widely distributed 90 kDa glycoprotein that is homologous to the Hermes-1 human lymphocyte homing receptor. J Immunol 143: 851, 1989PubMedGoogle Scholar
  9. 9.
    . Oostendorp RAJ, Reisbach G, Spitzer E, Thalmeier K, Dienemann H, Mergenthaler H-G, Dörmer P: VLA-4 and VCAM-1 are the principal adhesion molecules involved in the interaction between blast colony-forming cells and bone marrow stromal cells. Brit J Haematol, 97: 275, 1995CrossRefGoogle Scholar
  10. 10.
    . Denning SM, Telen MJ, Hale LP, Liao HX, Haynes BF: CD44 and CD44R cluster report. Leukocyte Typing V, Oxford University Press, 1995Google Scholar
  11. 11.
    . Voß C, Kremmer E, Hoffmann-Fezer G, Schumm M, Günther W, Kolb H-J, Thierfelder S: Identification and characterization of a mous monoclonal antibody (M10) against canine (dog) CD8+ lymphocytes. Vet Immunol Immunopathol 38: 311, 1993PubMedCrossRefGoogle Scholar
  12. 12.
    . Bruynzeel I, Koopman G, van der Raaij LMH, Pals ST, Willemze R: CD44 antibody stimulates adhesion of peripheral blood T cells to keratinocytes through the LFA-1/ICAM-1 pathway. J Invest Dermatol 100: 424, 1993PubMedCrossRefGoogle Scholar
  13. 13.
    . Toyama-Sorimachi N, Miyake K, Miyasaka M: Activation of CD44 induces ICAM-1/LFA-1-independent, Ca2+Mg2+-independent adhesion pathway in lymphocyte endothelial cell interaction. Eur J Immunol 23: 439, 1993PubMedCrossRefGoogle Scholar
  14. 14.
    . Galandrini R, Albi N, Tripodi G, Zarcone D, Terenzi A, Moretta A, Grossi CE, Velardi A: Antibodies to CD44 trigger effector functions of human T cell clones. J Immunol 150: 4225, 1993PubMedGoogle Scholar
  15. 15.
    . Gruber MF, Webb DSA, Gerrard TL: Stimulation of human monocytes via CD45, CD44, and LFA-3 triggers macrophage-colony-stimulating factor production. Synergism with Lipopolysaccharide and IL-1ß. J Immunol 148: 1113, 1992PubMedGoogle Scholar
  16. 16.
    . Galandrini R, Galluzzo E, Albi N, Grossi CE, Velardi A: Hyaluronate is costimulatory for human t cell effector functions and binds to CD44 on activated T cells. J Immunol 153: 21, 1994PubMedGoogle Scholar
  17. 17.
    . Lokeshwar VB, Bourguignon LYW: The lymphoma transmembrane glycoprotein gp85 (CD44) is a novel guanine nucleotide-binding protein which regulates gp85 (CD44)-ankyrin interaction. J Biol Chem 267: 2 2073, 1992PubMedGoogle Scholar
  18. 18.
    . Rothman BL, Kennure N, Kelley KA, Katz M, Aune TM: Elevation of intracellular cAMP in human T lymphocytes by an anti-CD44 mAb. J Immunol 151: 6036, 1993PubMedGoogle Scholar
  19. 19.
    . Mergenthaler H-G, Brühl P, Dörmer P: Kinetics of myeloid progenitor cells in human micro long-term bone marrow cultures. Exp Hematol 16: 145, 1988PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • Robert A. J. Oostendorp
    • 1
    • 2
    Email author
  • Elisabeth Spitzer
    • 1
  • Peter Dörmer
    • 1
  1. 1.GSF-Forschungszentrum für Umwelt und GesundheitInstitut für Experimentelle HämatologieMünchenGermany
  2. 2.GSF-Institut für Experimentelle HämatologieMünchenGermany

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