Engagement of human PECAM-1 (CD31) on human endothelial cells increases intracellular calcium ion concentration and stimulates prostacyclin release

J Clin Invest. 1998 Jan 1;101(1):212-22. doi: 10.1172/JCI269.

Abstract

Platelet-endothelial cell adhesion molecule-1 (PECAM-1) is a member of the immunoglobulin superfamily that plays a role in a number of endothelial cell (EC) functions including migration, angiogenesis, and transmigration of leukocytes across endothelium. We postulated that one way PECAM-1 might exert its effects was by regulating intracellular EC levels of calcium. Using single-cell fluorometry, we found that engagement of PECAM-1 by mAbs induced a slow but sustained increase in intracellular calcium, both in EC and in an adherent PECAM-1-transfected cell line that models endothelium. Generation of this signal was specific for certain anti-PECAM-1 antibodies, required the presence of the cytoplasmic domain, depended on extracellular calcium and on tyrosine phosphorylation, but did not require cross-linking; in fact, calcium increases were stimulated by certain Fab fragments. Activation of EC by PECAM-1 also caused a time-dependent increase in prostacyclin release. Given the importance of intracellular calcium and prostacyclin release as signaling molecules, engagement of PECAM-1 during cell-cell interactions may alter a number of EC functions including secretion of vasoactive mediators.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / pharmacology
  • Binding Sites
  • Calcium / metabolism*
  • Cations, Divalent
  • Cell Line
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Epitopes, B-Lymphocyte / immunology
  • Epoprostenol / metabolism*
  • Humans
  • Immunoglobulin Fab Fragments / metabolism
  • Immunoglobulin Fab Fragments / pharmacology
  • Mice
  • Phosphorylation
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism*
  • Structure-Activity Relationship
  • Transfection
  • Tyrosine / metabolism
  • Umbilical Veins / cytology

Substances

  • Antibodies, Monoclonal
  • Cations, Divalent
  • Epitopes, B-Lymphocyte
  • Immunoglobulin Fab Fragments
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Tyrosine
  • Epoprostenol
  • Calcium