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PMID: 1379610 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Role of beta 1 and beta 2 integrins in the adhesion of human CD34hi stem cells to bone marrow stroma.

The Journal of clinical investigation ·Vol. 90 ·No. 2 ·1992-08-00 ·Pages 358-67

Teixidó J, Hemler ME, Greenberger JS, Anklesaria P

Abstract

Hematopoietic stem cell interaction with elements of the underlying stroma is essential for sustained normal hematopoiesis. Here we have determined that adhesion receptors in the integrin family play a role in promoting adhesion of human hematopoietic stem cells to cultured human marrow stromal cells. Enriched CD34hi progenitor cells expressed VLA-4, VLA-5, and at least one or more beta 2 integrins. Homogeneous marrow stromal cell monolayers capable of supporting proliferation of cocultivated CD34hi cells expressed VCAM-1 and fibronectin (ligands for VLA-4 and VLA-5) as well as ICAM-1 (ligand for LFA-1 and Mac-1). Adhesion-blocking experiments indicated that VLA-4/VCAM-1, VLA-5/fibronectin, and beta 2-integrin/ICAM-1 pathways all are important for CD34hi cell attachment to stromal cells. Consistent with this suggestion, IL-1 stimulation of stromal cells caused both increased VCAM-1 and ICAM-1 expression and increased attachment by CD34hi bone marrow cells. In addition, CD34hi cells utilized VLA-4 to adhere to purified VCAM-1 and employed VLA-5 (and to a lesser extent VLA-4) to adhere to purified fibronectin. Together these results suggest that CD34hi stem cells may utilize multiple integrin-mediated adhesion pathways to localize within specialized microenvironmental niches created by marrow stromal cells.

MeSH Terms
Antigens, CD/analysis Antigens, CD34 Antigens, Differentiation, B-Lymphocyte/analysis Antigens, Differentiation, Myelomonocytic/analysis Bone Marrow Cells Cell Adhesion Cell Adhesion Molecules/metabolism Fibronectins/metabolism Flow Cytometry Hematopoiesis Hematopoietic Stem Cells/cytology,metabolism Humans In Vitro Techniques Integrins/physiology Receptors, Transferrin Receptors, Very Late Antigen/metabolism Sialic Acid Binding Ig-like Lectin 3 Vascular Cell Adhesion Molecule-1
Chemicals
Antigens, CD Antigens, CD34 Antigens, Differentiation, B-Lymphocyte Antigens, Differentiation, Myelomonocytic CD33 protein, human CD71 antigen Cell Adhesion Molecules Fibronectins Integrins Receptors, Transferrin Receptors, Very Late Antigen Sialic Acid Binding Ig-like Lectin 3 Vascular Cell Adhesion Molecule-1
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Teixidó J
Department of Tumor Virology, Dana Farber Cancer Institute, Boston, Massachusetts 02115.
Hemler M E
Greenberger J S
Anklesaria P
References (76)
76 references, click to expand
  1. Signaling by vascular cell adhesion molecule-1 (VCAM-1) through VLA-4 promotes CD3-dependent T cell proliferation.
    Eur J Immunol. 1991 Nov;21(11):2871-5 PMID: 1718763
  2. Adhesion of immature thymocytes to thymic stromal cells through fibronectin molecules and its significance for the induction of thymocyte differentiation.
    Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5685-9 PMID: 1829526
  3. Barrier cells: stromal regulation of hematopoiesis and blood cell release in normal and stressed murine bone marrow.
    Blood. 1991 Aug 15;78(4):975-90 PMID: 1868254
  4. Differentiation of primitive human multipotent hematopoietic progenitors into single lineage clonogenic progenitors is accompanied by alterations in their interaction with fibronectin.
    J Exp Med. 1991 Sep 1;174(3):693-703 PMID: 1875168
  5. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site.
    Cell. 1990 Feb 23;60(4):577-84 PMID: 1689216
  6. Human B lymphocytes define an alternative mechanism of adhesion to fibronectin. The interaction of the alpha 4 beta 1 integrin with the LHGPEILDVPST sequence of the type III connecting segment is sufficient to promote cell attachment.
    J Immunol. 1990 May 1;144(9):3361-6 PMID: 2139453
  7. Identification of distinctive stromal elements in erythroid and neutrophil granuloid spleen colonies: light and electron microscopic study.
    Exp Hematol. 1977 Nov;5(6):505-22 PMID: 73471
  8. Binding of the integrin Mac-1 (CD11b/CD18) to the third immunoglobulin-like domain of ICAM-1 (CD54) and its regulation by glycosylation.
    Cell. 1991 Jun 14;65(6):961-71 PMID: 1675157
  9. Adhesion of human B cells to germinal centers in vitro involves VLA-4 and INCAM-110.
    Science. 1990 Aug 31;249(4972):1030-3 PMID: 1697696
  10. Expression of the CD11/CD18, leukocyte adhesion molecule 1, and CD44 adhesion molecules during normal myeloid and erythroid differentiation in humans.
    Blood. 1990 Dec 15;76(12):2483-92 PMID: 1702327
  11. Human eosinophil, but not neutrophil, adherence to IL-1-stimulated human umbilical vascular endothelial cells is alpha 4 beta 1 (very late antigen-4) dependent.
    J Immunol. 1991 May 15;146(10):3419-23 PMID: 1709195
  12. Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules.
    J Exp Med. 1991 Jun 1;173(6):1553-7 PMID: 1709678
  13. Adhesion receptors of the immune system.
    Nature. 1990 Aug 2;346(6283):425-34 PMID: 1974032
  14. Evidence for a role of the integrin VLA-4 in lympho-hemopoiesis.
    J Exp Med. 1991 Mar 1;173(3):599-607 PMID: 1997648
  15. Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1.
    Blood. 1991 Jul 1;78(1):55-62 PMID: 2070060
  16. A new hematopoietic cell line, KMT-2, having human interleukin-3 receptors.
    Blood. 1990 Aug 1;76(3):501-7 PMID: 2198959
  17. Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor alpha 4 beta 1.
    Cell. 1990 Jan 12;60(1):53-61 PMID: 2295088
  18. Cell-cell adhesion mediated by binding of membrane-anchored transforming growth factor alpha to epidermal growth factor receptors promotes cell proliferation.
    Proc Natl Acad Sci U S A. 1990 May;87(9):3289-93 PMID: 2333283
  19. Thrombospondin functions as a cytoadhesion molecule for human hematopoietic progenitor cells.
    Blood. 1990 Jun 15;75(12):2311-8 PMID: 2350577
  20. Molecular basis of the recognition of intravenously transplanted hemopoietic cells by bone marrow.
    Proc Natl Acad Sci U S A. 1988 May;85(9):3180-3 PMID: 2452446
  21. Analysis of fibronectin receptor function with monoclonal antibodies: roles in cell adhesion, migration, matrix assembly, and cytoskeletal organization.
    J Cell Biol. 1989 Aug;109(2):863-75 PMID: 2527241
  22. Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin.
    J Cell Biol. 1989 Sep;109(3):1321-30 PMID: 2527858
  23. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes.
    Cell. 1989 Dec 22;59(6):1203-11 PMID: 2688898
  24. An in vitro limiting-dilution assay of long-term repopulating hematopoietic stem cells in the mouse.
    Blood. 1989 Dec;74(8):2755-63 PMID: 2819245
  25. Vascular cell adhesion molecule-1 and the integrin VLA-4 mediate adhesion of human B cell precursors to cultured bone marrow adherent cells.
    J Clin Invest. 1991 Sep;88(3):995-1004 PMID: 1715889
  26. Coexpression of two fibronectin receptors, VLA-4 and VLA-5, by immature human erythroblastic precursor cells.
    J Clin Invest. 1991 Jan;87(1):6-11 PMID: 1824634
  27. Fibronectin and VLA-4 in haematopoietic stem cell-microenvironment interactions.
    Nature. 1991 Aug 1;352(6334):438-41 PMID: 1861722
  28. Interferon-alpha overrides the deficient adhesion of chronic myeloid leukemia primitive progenitor cells to bone marrow stromal cells.
    Blood. 1991 Jul 15;78(2):499-505 PMID: 1906352
  29. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis.
    Science. 1991 Feb 15;251(4995):788-91 PMID: 1990440
  30. Hemonectin mediates adhesion of engrafted murine progenitors to a clonal bone marrow stromal cell line from Sl/Sld mice.
    Blood. 1991 Apr 15;77(8):1691-8 PMID: 2015397
  31. Structure of the integrin VLA-4 and its cell-cell and cell-matrix adhesion functions.
    Immunol Rev. 1990 Apr;114:45-65 PMID: 2142475
  32. Expression of integrins in human bone marrow.
    Br J Haematol. 1990 Nov;76(3):323-32 PMID: 2261342
  33. Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers.
    Proc Natl Acad Sci U S A. 1990 May;87(9):3584-8 PMID: 2333304
  34. VLA-3: a novel polypeptide association within the VLA molecular complex: cell distribution and biochemical characterization.
    Eur J Immunol. 1986 Nov;16(11):1343-9 PMID: 2430809
  35. Circulation of CD34+ hematopoietic stem cells in the peripheral blood of high-dose cyclophosphamide-treated patients: enhancement by intravenous recombinant human granulocyte-macrophage colony-stimulating factor.
    Blood. 1989 Nov 1;74(6):1905-14 PMID: 2478216
  36. An inducible endothelial cell surface glycoprotein mediates melanoma adhesion.
    Science. 1989 Dec 8;246(4935):1303-6 PMID: 2588007
  37. Multilineage hemopoiesis induced by cloned stromal cells.
    Int J Cell Cloning. 1989 Nov;7(6):373-84 PMID: 2809273
  38. The function of multiple extracellular matrix receptors in mediating cell adhesion to extracellular matrix: preparation of monoclonal antibodies to the fibronectin receptor that specifically inhibit cell adhesion to fibronectin and react with platelet glycoproteins Ic-IIa.
    J Cell Biol. 1988 Nov;107(5):1881-91 PMID: 2846588
  39. Dual role of fibronectin in hematopoietic differentiation.
    Blood. 1989 Jan;73(1):111-6 PMID: 2910353
  40. Fibronectin and its receptors.
    Annu Rev Biochem. 1988;57:375-413 PMID: 2972252
  41. Simian virus 40-transformed adherent cells from human long-term marrow cultures: cloned cell lines produce cells with stromal and hematopoietic characteristics.
    Blood. 1987 Aug;70(2):464-74 PMID: 3038214
  42. Cells with marrow and spleen repopulating ability and forming spleen colonies on day 16, 12, and 8 are sequentially ordered on the basis of increasing rhodamine 123 retention.
    J Cell Physiol. 1988 Sep;136(3):531-6 PMID: 3170649
  43. In vitro homing of hemopoietic stem cells is mediated by a recognition system with galactosyl and mannosyl specificities.
    Proc Natl Acad Sci U S A. 1987 Jul;84(13):4485-9 PMID: 3474617
  44. Characterization of the cell surface heterodimer VLA-4 and related peptides.
    J Biol Chem. 1987 Aug 25;262(24):11478-85 PMID: 3497921
  45. Differential binding of erythroid and myeloid progenitors to fibroblasts and fibronectin.
    Blood. 1987 Jun;69(6):1587-94 PMID: 3580569
  46. Generation of functional clonal cell lines from human bone marrow stroma.
    Proc Natl Acad Sci U S A. 1985 May;82(10):3477-80 PMID: 3858834
  47. Cell surface antigens of human bladder cancer defined by mouse monoclonal antibodies.
    Proc Natl Acad Sci U S A. 1984 Jan;81(1):224-8 PMID: 6364135
  48. The essential cells of the hemopoietic microenvironment.
    Exp Hematol. 1984 Aug;12(7):517-21 PMID: 6745328
  49. Identification of multiple cell adhesion receptors for collagen and fibronectin in human fibrosarcoma cells possessing unique alpha and common beta subunits.
    J Cell Biol. 1987 Oct;105(4):1873-84 PMID: 2822727
  50. Number and continuous proliferative pattern of transplanted primitive immunohematopoietic stem cells.
    Proc Natl Acad Sci U S A. 1988 Feb;85(3):822-6 PMID: 2893377
  51. Heparan sulphate bound growth factors: a mechanism for stromal cell mediated haemopoiesis.
    Nature. 1988 Mar 24;332(6162):376-8 PMID: 2965305
  52. Heparan sulfate is necessary for adhesive interactions between human early hemopoietic progenitor cells and the extracellular matrix of the marrow microenvironment.
    Leukemia. 1988 Dec;2(12):804-9 PMID: 2974104
  53. Integrins: a family of cell surface receptors.
    Cell. 1987 Feb 27;48(4):549-54 PMID: 3028640
  54. Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor.
    Cell. 1985 Jan;40(1):191-8 PMID: 3155652
  55. Experimental models for understanding B lymphocyte formation.
    Adv Immunol. 1987;41:181-267 PMID: 3318292
  56. Altered adhesive interactions with marrow stroma of haematopoietic progenitor cells in chronic myeloid leukaemia.
    Nature. 1987 Jul 23-29;328(6128):342-4 PMID: 3474529
  57. Compartmentalization of a haematopoietic growth factor (GM-CSF) by glycosaminoglycans in the bone marrow microenvironment.
    Nature. 1987 Mar 26-Apr 1;326(6111):403-5 PMID: 3494201
  58. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1.
    J Immunol. 1986 Aug 15;137(4):1270-4 PMID: 3525675
  59. Presence of alkaline-phosphatase-positive reticulum cells in fetal liver and bone marrow of mice and their absence in yolk sac.
    Exp Hematol. 1986 Sep;14(8):705-9 PMID: 3743676
  60. Blast cell colony assay for umbilical cord blood and adult bone marrow progenitors.
    Blood. 1987 Mar;69(3):953-6 PMID: 3814825
  61. Glycoproteins of 210,000 and 130,000 m.w. on activated T cells: cell distribution and antigenic relation to components on resting cells and T cell lines.
    J Immunol. 1984 Jun;132(6):3011-8 PMID: 6327814
  62. Characterization of a novel differentiation antigen complex recognize by a monoclonal antibody (A-1A5): unique activation-specific molecular forms on stimulated T cells.
    J Immunol. 1983 Jul;131(1):334-40 PMID: 6408178
  63. Definition of a common leukocyte cell-surface antigen (Lp95-150) associated with diverse cell-mediated immune functions.
    J Immunol. 1983 Dec;131(6):2913-8 PMID: 6644024
  64. Evidence for structured variation in self-renewal capacity within long-term bone marrow cultures.
    Proc Natl Acad Sci U S A. 1980 May;77(5):2927-30 PMID: 6930675
  65. Hybrid cell lines secreting monoclonal antibody specific for major histocompatibility antigens of the mouse.
    Nature. 1978 Jan 19;271(5642):249-51 PMID: 74805
  66. Regulation of haemopoietic stem cell proliferation in long term bone marrow cultures.
    Biomedicine. 1977 Dec;27(9-10):344-9 PMID: 606310
  67. Molecules and structures involved in the adhesion of natural killer cells to vascular endothelium.
    J Exp Med. 1991 Feb 1;173(2):439-48 PMID: 1671081
  68. Characterization of ICAM-2 and evidence for a third counter-receptor for LFA-1.
    J Exp Med. 1991 Jul 1;174(1):253-67 PMID: 1676048
  69. Inducible cell adhesion molecule 110 (INCAM-110) is an endothelial receptor for lymphocytes. A CD11/CD18-independent adhesion mechanism.
    J Exp Med. 1990 Apr 1;171(4):1369-74 PMID: 1691264
  70. Identification of surface proteins mediating adherence of CD11/CD18-deficient lymphoblastoid cells to cultured human endothelium.
    J Clin Invest. 1990 Jun;85(6):2019-22 PMID: 1693380
  71. Identification of a ligand for the c-kit proto-oncogene.
    Cell. 1990 Oct 5;63(1):167-74 PMID: 1698553
  72. Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38- progenitor cells.
    Blood. 1991 Mar 15;77(6):1218-27 PMID: 1705833
  73. Transmembrane form of the kit ligand growth factor is determined by alternative splicing and is missing in the Sld mutant.
    Cell. 1991 Mar 8;64(5):1025-35 PMID: 1705866
  74. Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells.
    Blood. 1991 May 15;77(10):2142-9 PMID: 1709371
  75. Effect of a new monoclonal antibody, TA-2, that inhibits lymphocyte adherence to cytokine stimulated endothelium in the rat.
    J Immunol. 1991 Jul 1;147(1):109-16 PMID: 1711066
  76. Tumor cell surface alpha 4 beta 1 integrin mediates adhesion to vascular endothelium: demonstration of an interaction with the N-terminal domains of INCAM-110/VCAM-1.
    Cell Regul. 1991 May;2(5):347-55 PMID: 1716464
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI115870
Published
1992-08-00
Pages
358-67
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC443110
Subset
IM
Grants
NCI NIH HHS · CA-39851 · United States
NCI NIH HHS · CA42368 · United States
NIDCR NIH HHS · DE-08798 · United States
External Links
PubMed source DOI: 10.1172/JCI115870 PMC Full Text View journal details
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