The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice

Blood. 2000 Jun 1;95(11):3289-96.

Abstract

Hematopoietic stem cell homing and engraftment require several adhesion interactions, which are not fully understood. Engraftment of nonobese/severe combined immunodeficiency (NOD/SCID) mice by human stem cells is dependent on the major integrins very late activation antigen-4 (VLA-4); VLA-5; and to a lesser degree, lymphocyte function associated antigen-1 (LFA-1). Treatment of human CD34(+) cells with antibodies to either VLA-4 or VLA-5 prevented engraftment, and treatment with anti-LFA-1 antibodies significantly reduced the levels of engraftment. Activation of CD34(+) cells, which bear the chemokine receptor CXCR4, with stromal derived factor 1 (SDF-1) led to firm adhesion and transendothelial migration, which was dependent on LFA-1/ICAM-1 (intracellular adhesion molecule-1) and VLA-4/VCAM-1 (vascular adhesion molecule-1). Furthermore, SDF-1-induced polarization and extravasation of CD34(+)/CXCR4(+) cells through the extracellular matrix underlining the endothelium was dependent on both VLA-4 and VLA-5. Our results demonstrate that repopulating human stem cells functionally express LFA-1, VLA-4, and VLA-5. Furthermore, this study implies a novel approach to further advance clinical transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Antigens, CD34
  • Cell Adhesion
  • Cells, Cultured
  • Chemokine CXCL12
  • Chemokines, CXC / pharmacology*
  • Chemotaxis
  • Endothelium, Vascular / physiology*
  • Fetal Blood / cytology
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Infant, Newborn
  • Integrin alpha4beta1
  • Integrin beta1 / physiology
  • Integrins / antagonists & inhibitors
  • Integrins / physiology*
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Lymphocyte Function-Associated Antigen-1 / physiology*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Models, Biological
  • Receptors, Fibronectin / antagonists & inhibitors
  • Receptors, Fibronectin / physiology*
  • Receptors, Lymphocyte Homing / antagonists & inhibitors
  • Receptors, Lymphocyte Homing / physiology*
  • Stromal Cells / physiology*
  • Transplantation, Heterologous / immunology*

Substances

  • Antibodies
  • Antigens, CD34
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • Integrin alpha4beta1
  • Integrin beta1
  • Integrins
  • Lymphocyte Function-Associated Antigen-1
  • Receptors, Fibronectin
  • Receptors, Lymphocyte Homing