Alpha 4 beta 1 and alpha 5 beta 1 are differentially expressed during myelopoiesis and mediate the adherence of human CD34+ cells to fibronectin in an activation-dependent way

Blood. 1993 Jan 15;81(2):344-51.

Abstract

To study the receptors involved in the interaction between extracellular matrix proteins and hematopoietic progenitor cells, we analyzed the expression of beta 1 integrins on CD34+ bone marrow cells by means of immunoflowcytometry. Alpha 4 beta 1 and alpha 5 beta 1 were expressed, whereas alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 1, and alpha v beta 1 were virtually absent. Furthermore, we assessed the alpha 4 and alpha 5 expression on committed myeloid progenitor cells. These colony-forming cells were detected in the alpha 4 dull fraction and the alpha 5 dull fraction. During myeloid differentiation, both in vivo and in vitro, a differential expression of alpha 4 beta 1 and alpha 5 beta 1 was observed. alpha 5 beta 1 was found to be lost at the myelocytic-metamyelocytic stage, before the loss of alpha 4 beta 1, at the band stage. Functional studies showed no binding of erythroid progenitor-depleted, CD34+ bone marrow cells to fibronectin. However, protein kinase C activation strongly induced fibronectin binding (68% of the cells). Inhibition experiments with specific antibodies and peptides showed the binding to be mediated by both alpha 4 beta 1 and alpha 5 beta 1. Also, colony-forming cells of granulocytes and macrophages were demonstrated to adhere to fibronectin in an activation-dependent way. During granulocyte colony-stimulating factor-induced in vitro maturation, the activation-dependent fibronectin binding capacity is gradually lost. We conclude that: (1) CD34+ bone marrow cells express alpha 4 beta 1 and alpha 5 beta 1; (2) the expression of alpha 4 beta 1 and alpha 5 beta 1 is differentially expressed during myeloid differentiation; and (3) binding of CD34+ bone marrow cells to fibronectin is activation dependent.

MeSH terms

  • Antibodies, Monoclonal
  • Antigens, CD / analysis*
  • Antigens, CD / physiology*
  • Antigens, CD34
  • Bone Marrow / physiology*
  • Bone Marrow Cells
  • Cell Adhesion* / drug effects
  • Colony-Forming Units Assay
  • Fibronectins / metabolism*
  • HLA-DR Antigens / analysis
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Integrins / immunology
  • Integrins / physiology*
  • Reference Values
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, CD34
  • Fibronectins
  • HLA-DR Antigens
  • Integrins
  • Tetradecanoylphorbol Acetate