PECAM-1 (CD31) is required for interactions of platelets with endothelial cells after irradiation.
Sustained adhesion of platelets to endothelial cells (EC) is believed to contribute to thrombosis and vascular occlusions following radiation exposure leading to organ functional impairment and even death. Our objective was to evaluate the role of platelet endothelial cell adhesion molecule (PECAM)-1 in the prothrombotic response of EC after irradiation. Endothelial PECAM-1 expression was determined by cell-enzyme linked immunosorbent assay (ELISA) on human microvascular EC from lung (HMVEC-L) up to 21 days after a 10 Gy irradiation. Platelet- and leukocyte-endothelial cell interactions were assessed using a flow adhesion assay with fluorescently labeled whole blood, and the function of PECAM-1 in these processes was measured by using blocking antibody. PECAM-1 expression was significantly increased on irradiated HMVEC-L and remained elevated at 21 days. Anti-PECAM-1 antibody significantly inhibited adhesion of single platelets and thrombi on irradiated HMVEC-L. This inhibitory effect persisted at day 21. Anti-PECAM-1 also reduced leukocyte adhesion to irradiated HMVEC-L. The up-regulation of endothelial PECAM-1 following radiation exposure is persistent. PECAM-1 plays a key role platelet adhesion/aggregation on irradiated EC. Therefore, strategies targeting this adhesion molecule may prevent the development of radiation pathologies.
Gaugler
M-H
MH
Institut de Radioprotection et de Surete Nuclèaire, IRSN, DRPH/SRBE/LRPAT, Fontenay-aux-Roses, France. marie-helene.gaugler@irsn.fr
Vereycken-Holler
V
V
Squiban
C
C
Aigueperse
J
J
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology*; D002448:Cell Adhesion / Q000528:radiation effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology* / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D007962:Leukocytes / Q000166:cytology; D008168:Lung / Q000098:blood supply; D008833:Microcirculation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology / Q000502:physiology* / Q000528:radiation effects; D019851:Thrombophilia / Q000209:etiology; D015854:Up-Regulation / Q000528:radiation effects
D000911:Antibodies, Monoclonal; D019408:Platelet Endothelial Cell Adhesion Molecule-1