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Intercellular adhesion molecule-4 binds alpha(4)beta(1) and alpha(V)-family integrins through novel integrin-binding

F A Spring1, S F Parsons, S Ortlepp

  • 1Bristol Institute for Transfusion Sciences, United Kingdom. fran.spring@nbs.nhs.uk

Blood
|July 4, 2001
PubMed

Insights

Intercellular Adhesion Molecule 4 (ICAM-4) binds to novel integrins on red blood cells and other cells. This finding reveals ICAM-4

Area of Science:

  • Cell Adhesion and Signaling
  • Hematology and Immunology
  • Molecular and Structural Biology

Background:

  • ICAM-4 (Intercellular Adhesion Molecule 4) is an LW blood group glycoprotein expressed in erythroid cells.
  • Its precise function and ligand-binding interactions within the intercellular adhesion molecule (ICAM) family were previously unclear.
  • Understanding ICAM-4's role is crucial for erythropoiesis and potentially sickle cell disease.

Purpose of the Study:

  • To identify ligands for ICAM-4 on hemopoietic and nonhemopoietic cell lines.
  • To elucidate the specific integrins mediating cell adhesion to ICAM-4.
  • To investigate the structural basis of ICAM-4's integrin-binding interactions.

Main Methods:

  • Utilized peptide and antibody inhibition studies to identify mediating integrins.
  • Employed cell line adhesion assays with ICAM-4-Fc constructs.
  • Modeled ICAM-4 structure based on ICAM-2 and performed site-directed mutagenesis.

Main Results:

  • Adhesion to ICAM-4 was mediated by an LDV-inhibitable integrin (alpha(4)beta(1)) on hemopoietic cells.
  • Adhesion was mediated by RGD-inhibitable alpha(V) integrins (alpha(V)beta(1), alpha(V)beta(5)) on nonhemopoietic cells.
  • Neither LETS nor LDV motifs in ICAM-4's first domain were critical for integrin binding, suggesting novel binding sites.

Conclusions:

  • ICAM-4 is the first ICAM member identified as a ligand for non-beta(2) integrins.
  • ICAM-4 possesses unique integrin-binding site(s) distinct from other ICAMs.
  • Findings suggest a role for ICAM-4 in normal erythropoiesis and adhesive interactions in sickle cells.

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