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

J Clin Invest. 1992 Aug;90(2):358-67. doi: 10.1172/JCI115870.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / analysis*
  • Antigens, CD34
  • Antigens, Differentiation, B-Lymphocyte / analysis
  • Antigens, Differentiation, Myelomonocytic / analysis
  • Bone Marrow Cells*
  • Cell Adhesion Molecules / metabolism
  • Cell Adhesion*
  • Fibronectins / metabolism
  • Flow Cytometry
  • Hematopoiesis*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / 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

Substances

  • 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