P-selectin promotes neutrophil extracellular trap formation in mice.

ETULAIN, J; MARTINOD, K; WONG, SL; CIFUNI, SM; SCHATTNER, M; WAGNER, DD

BLOOD, THE JOURNAL OF THE AMERICAN SOCIETY OF HEMATOLOGY - PRINT

AMER SOC HEMATOLOGY

Lugar: Washington; Año: 2015 vol. 126 p. 242 - 246

0006-4971

Neutrophil extracellular traps (NETs) are released in the vasculature. Besides trapping microbes, they promote inflammatory and thrombotic diseases. Considering that P-selectin induces prothrombotic and proinflammatory signaling, we studied the role of this selectin in NET formation. NET release (NETosis) was induced by thrombin-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 not induced by platelets from P-selectin-/- mice. Moreover, NETosis was also promoted by P-selectin-Ig fusion protein but not by control Ig. We isolated neutrophils from mice engineered to overproduce soluble P-selectin, the P-selectinΔCT/ΔCT mice. While 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 formation after stimulation with PAF, ionomycin, or PMA was significantly enhanced, indicating that the P-selectinΔCT/ΔCT 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.