Platelet endothelial cell adhesion molecule-1 signaling inhibits the activation of human platelets

Milenko Cicmil, Jo Stevens, Mireille Leduc, Cassian Bon, Jonathan M Gibbins

Research output: Contribution to journalArticlepeer-review

Abstract

Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is a 130-kd transmembrane glycoprotein and a member of the growing family of receptors with immunoreceptor tyrosine-based inhibitory motifs (ITIMs). PECAM-1 is expressed on platelets, certain T cells, monocytes, neutrophils, and vascular endothelial cells and is involved in a range of cellular processes, though the role of PECAM-1 in platelets is unclear. Cross-linking of PECAM-1 results in phosphorylation of the ITIM allowing the recruitment of signaling proteins that bind by way of Src-homology domain 2 interactions. Proteins that have been implicated in the negative regulation of cellular activation by ITIM-bearing receptors include the tyrosine phosphatases SHP-1 and SHP-2. Tyrosine phosphorylation of immunoreceptor tyrosine-based activatory motif (ITAM)-bearing receptors such as the collagen receptor GPVI-Fc receptor gamma-chain complex on platelets leads to activation. Increasing evidence suggests that ITIM- and ITAM-containing receptors may act antagonistically when expressed on the same cell. In this study it is demonstrated that cross-linking PECAM-1 inhibits the aggregation and secretion of platelets in response to collagen and the GPVI-selective agonist convulxin. In these experiments thrombin-mediated platelet aggregation and secretion were also reduced, albeit to a lesser degree than for collagen, suggesting that PECAM-1 function may not be restricted to the inhibition of ITAM-containing receptor pathways. PECAM-1 activation also inhibited platelet protein tyrosine phosphorylation stimulated by convulxin and thrombin; this was accompanied by inhibition of the mobilization of calcium from intracellular stores. These data suggest that PECAM-1 may play a role in the regulation of platelet function in vivo.
Original languageEnglish
Pages (from-to)137-44
Number of pages8
JournalBlood
Volume99
Issue number1
Publication statusPublished - 1 Jan 2002

Keywords

  • Antibodies
  • Antigens, CD31
  • Binding Sites
  • Blood Platelets
  • Calcium
  • Collagen
  • Cross-Linking Reagents
  • Crotalid Venoms
  • Cytoplasmic Granules
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Immunoglobulin Fab Fragments
  • Immunoglobulin G
  • Lectins, C-Type
  • Phosphorylation
  • Phosphotyrosine
  • Platelet Activation
  • Signal Transduction
  • Thrombin

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