info:eu-repo/semantics/article
P-selectin promotes neutrophil extracellular trap formation in mice
Fecha
2015-07Registro en:
Etulain, Julia; Martinod, Kimberly; Wong, Siu Ling; Cifuni, Stephen M.; Schattner, Mirta Ana; et al.; P-selectin promotes neutrophil extracellular trap formation in mice; American Society of Hematology; Blood; 126; 2; 7-2015; 242-246
0006-4971
CONICET Digital
CONICET
Autor
Etulain, Julia
Martinod, Kimberly
Wong, Siu Ling
Cifuni, Stephen M.
Schattner, Mirta Ana
Wagner, Denisa D.
Resumen
Neutrophil extracellular traps(NETs)canbereleased in thevasculature. Inaddition totrapping microbes, they promote inflammatory and thrombotic diseases. Considering that P-selectin induces prothrombotic and proinflammatory signaling, we studied the role of this selectin in NETformation.NETformation(NETosis)wasinducedbythrombin-activated platelets rosetting with neutrophils and was inhibited by anti-P-selectin aptamer or anti-P-selectin glycoprotein ligand-1 (PSGL-1) inhibitory antibody but was not induced by platelets from P-selectin2/2 mice. Moreover, NETosis was also promoted by P-selectinimmunoglobulin fusion protein butnotby control immunoglobulin.We isolatedneutrophils frommice engineered tooverproduce soluble P-selectin (P-selectinDCT/DCT mice). Although the levels of circulating DNA and nucleosomes (indicative of spontaneous NETosis) were normal in these mice, basal neutrophil histone citrullination and presence of P-selectin on circulating neutrophils were elevated. NET formationafter stimulationwithplatelet activatingfactor, ionomycin,orphorbol 12-myristate 13-acetatewassignificantlyenhanced, indicating that the P-selectinDCT/DCT neutrophils were primed for NETosis. In summary, P-selectin, cellular or soluble, through binding to PSGL-1, promotes NETosis, suggesting that this pathway is a potential therapeutic target for NET-related diseases.