Cell
Volume 60, Issue 4, 23 February 1990, Pages 577-584
Journal home page for Cell

VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/Fibronectin binding site

https://doi.org/10.1016/0092-8674(90)90661-WGet rights and content

Abstract

Cytokine-activated human endothelial cells express vascular cell adhesion molecule-1 (VCAM-1), which binds lymphocytes. We now identify the integrin VLA-4 as a receptor for VCAM-1 because VLA-4 surface expression on K-562 cells (following transfection of the VLA α4 subunit cDNA) resulted in specific cell adhesion to VCAM-1, and anti VLM4 antibodies completely inhibited VCAM-1-dependent cell-cell attachment. In addition, VLA-4 expression allowed K562 cells to attach to the heparin 11 binding region (FN-40) of fibronectin. However, VLA-41VCAM-1 and VLA-4/FN-40 interactions are readily distinguishable: only the former was inhibited by the anti VLA-4 monoclonal antibody HP1/3, and only the latter was inhibited by soluble FN40. The VCAM-1/VLA-4 ligand-receptor pair may play a major role in the recruitment of mononuclear leukocytes to inflammatory sites in vivo.

References (51)

  • M.D. Pierschbacher et al.

    Location of the cell-attachment site in fibronectin with monoclonal antibodies and proteolytic fragments of the molecule

    Cell

    (1981)
  • D.C. Anderson et al.

    Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins

    Annu. Rev. Med.

    (1987)
  • J. Bednarczyk et al.

    A monoclonal antibody to VLA-4 a chain (CDw49).induces homotypic lymphocyte aggregation

    J. Immunol.

    (1990)
  • E.L. Berg et al.

    Homing receptors and vascular addressins: cell adhesion molecules that direct lymphocyte traffic

    Immunol. Rev.

    (1989)
  • M.P. Bevilacqua et al.

    Identification of an inducible endothelialleukocyte adhesion molecule

  • M.P. Bevilacqua et al.

    Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins

    Science

    (1989)
  • A.W. Boyd et al.

    Intercellular adhesion molecule 1 (ICAM-1) has a central role in cellcell contact-mediated immune mechanisms

  • C. Clayberger et al.

    Identification and characterization of two novel lymphocyte function-associated antigens, L24 and L25

    J. Immunol.

    (1987)
  • T. Collins et al.

    Recombinant human tumour necrosis factor increases mRNA levels and surface expression of HLA-A,B antigens in vascular endothelial cells and dermal fibroblasts in vitro

  • M.L. Dustin et al.

    Lymphocyte functionassociated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells

    J. Cell Biol.

    (1988)
  • M.L. Dustin et al.

    Linkage between the T cell antigen receptor and LFA-1 regulates adhesion and deadhesion

    Nature

    (1989)
  • M.L. Dustin et al.

    Induction by II-1 and interferon-y: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1)

    J. Immunol.

    (1986)
  • Y. Fradet et al.

    Cell surface antigens of human bladder cancer defined by mouse monoclonal antibodies

  • H.P. Godfrey et al.

    Production of a fibronectin-associated lymphokine by cloned mouse T cells

    J. Immunol.

    (1988)
  • H. Groux et al.

    Suppressor effects and cyclic AMP accumulation by the CD29 molecule of CD4+ lymphocytes

    Nature

    (1989)
  • Cited by (0)

    View full text