Platelets induce human umbilical vein endothelial cell proliferation through P-selectin.
We studied whether platelets could participate in the endothelial cell monolayer regeneration in the case of a vessel damage. Incorporation of [3H]-thymidine into the DNA of human umbilical vein endothelial cells (HUVECs) was measured after 48 h of co-incubation with platelets. The effect of platelets was compared to that of platelet-free supernatants from thrombin-activated platelets that had secreted their active granule constituents. Platelets dose-dependently induced HUVEC proliferation. Platelets preactivated by thrombin induced similar proliferation as did unactivated platelets (proliferation factor = 7 - 8), indicating that preactivation of platelets was not required. Platelets fixed with paraformaldehyde had no effect, suggesting that the platelet mitogenic effect required a mobile, alive membrane. Ketanserine and suramin reduced by at most 30 % the platelet-induced proliferation; supernatants of thrombin-activated platelets caused only minor proliferation (proliferation factor = 2), suggesting that secreted 5-hydroxytryptamine and growth factors poorly contributed to the proliferative effect. When the co-incubation was performed in the presence of an anti P-selectin antibody, the platelet-induced HUVEC proliferation was inhibited. The results suggest that platelet adhesion participate in the control of the endothelial regeneration and that platelet P-selectin is a molecular determinant of the proliferative signal.
Marcondes
S
S
U428 INSERM, Faculté de Pharmacie, UFR des Sciences Pharmaceutiques et Biologiques, Paris, France.
Lafay
M
M
Brohard-Bohn
B
B
de Nucci
G
G
Rendu
F
F
D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology*; D005260:Female; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology; D019007:P-Selectin / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011247:Pregnancy; D012701:Serotonin / Q000502:physiology; D013498:Suramin / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
D008934:Mitogens; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D012701:Serotonin; D013498:Suramin; D007650:Ketanserin; D013917:Thrombin; D001241:Aspirin; D013936:Thymidine