Engagement of human PECAM-1 (CD31) on human endothelial cells increases intracellular calcium ion concentration and stimulates prostacyclin release.
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.
Gurubhagavatula
I
I
Pulmonary and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.
Amrani
Y
Y
Pratico
D
D
Ruberg
F L
FL
Albelda
S M
SM
Panettieri
R A
RA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D011464:Epoprostenol / Q000378:metabolism*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
D000911:Antibodies, Monoclonal; D002413:Cations, Divalent; D018985:Epitopes, B-Lymphocyte; D007140:Immunoglobulin Fab Fragments; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014443:Tyrosine; D011464:Epoprostenol; D002118:Calcium