Fibrinogen interactions with ICAM-1 (CD54) regulate endothelial cell survival

Area of Science:

• Cell Biology
• Molecular Biology
• Immunology

Background:

• Cellular adhesion molecules play critical roles in biological processes.
• Interactions between fibrinogen (Fg) and intercellular adhesion molecule 1 (ICAM-1) are implicated in cellular functions.

Purpose of the Study:

• To investigate the hypothesis that Fg-ICAM-1 interaction mediates cellular adhesion and proliferation.
• To elucidate the molecular mechanisms underlying Fg-ICAM-1-mediated endothelial cell survival.

Main Methods:

• Endothelial cells were treated with tumor necrosis factor (TNF)alpha.
• Fg:ICAM-1 ligation was induced, and its effects on extracellular signal-regulated kinase (ERK)-1/2 phosphorylation were assessed.
• Cell survival was evaluated using annexin V binding assays.
• The role of the cytoskeleton and specific signaling inhibitors (PD 98059) were investigated.
• Expression of cell survival factor A1 was analyzed.

Main Results:

• Fg:ICAM-1 ligation mediated endothelial cell survival and exhibited anti-apoptotic effects.
• Ligation led to hyperphosphorylation of ERK-1/2 in TNFalpha-treated endothelial cells, dependent on an intact cytoskeleton.
• Specific peptides Fg-gamma-(117-133) and ICAM-1(8-22) confirmed the specificity of ERK-1/2 phosphorylation.
• Cell attachment to Fg or Fg-gamma-(117-133) promoted survival, an effect blocked by ICAM-1(8-22).
• Inhibition of MEK-1 or dominant-negative ERK-1/2 led to apoptosis despite Fg:ICAM-1 ligation.
• Cell survival factor A1 was upregulated upon Fg adhesion, an effect blocked by ICAM-1(8-22) and PD 98059.

Conclusions:

• Fg:ICAM-1 ligation is a key pathway for endothelial cell survival.
• This pathway is mediated through the activation and upregulation of ERK-1/2 and cell survival factor A1.
• The findings highlight a novel survival mechanism involving Fg, ICAM-1, and the MAP kinase pathway.