Identification of an active sequence within the first immunoglobulin domain of intercellular cell adhesion molecule-1

S E D'Souza1, V J Byers-Ward, E E Gardiner

  • 1Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

Insights

Monocytic cells use integrin alphaMbeta2 to bind fibrinogen (fg). This interaction enhances cell adhesion to endothelial cells via intercellular adhesion molecule-1 (ICAM-1), with a specific peptide region identified as key.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Monocytic cells adhere to endothelial cells, a process crucial for immune responses.
  • Fibrinogen (fg) binding to monocytic cells via integrin alphaMbeta2 enhances this adhesion.
  • Intercellular adhesion molecule-1 (ICAM-1) plays a role in fg-mediated monocytic cell adhesion to endothelial cells.

Purpose of the Study:

  • To investigate the direct interaction between fibrinogen (fg) and intercellular adhesion molecule-1 (ICAM-1).
  • To identify specific regions within ICAM-1 and fg involved in their interaction.
  • To differentiate fg interactions with stimulated versus resting endothelial cells.

Main Methods:

  • Investigated direct binding of fg to intact and truncated forms of ICAM-1.
  • Utilized peptide mapping to identify the fg-binding site on ICAM-1 (ICAM-1-(8-21)).
  • Employed fg fragments and peptides (fg-gamma-117-133) to confirm binding specificity.
  • Assessed the role of ICAM-1-(8-21) and fg-gamma-117-133 in blocking cell adhesion.

Main Results:

  • A direct interaction between fg and ICAM-1 was demonstrated.
  • The peptide sequence ICAM-1-(8-21) within the first Ig domain of ICAM-1 specifically binds to fg fragments (X, D100, D80) but not fragment E.
  • The fg gamma-chain peptide (fg-gamma-117-133) blocked fg interaction with ICAM-1-(8-21).
  • ICAM-1-(8-21) peptide and anti-ICAM-1-(8-21) antibodies inhibited fg-mediated adhesion of ICAM-1-bearing cells.

Conclusions:

  • The ICAM-1-(8-21) region is a critical contact site for fg binding.
  • The fg gamma-chain peptide fg-gamma-117-133 is also involved in this interaction.
  • These specific molecular interactions mediate fg-ICAM-1-dependent monocytic cell adhesion.

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