P-selectin promotes neutrophil extracellular trap formation in mice

Blood. 2015 Jul 9;126(2):242-6. doi: 10.1182/blood-2015-01-624023. Epub 2015 May 15.


Neutrophil extracellular traps (NETs) can be released in the vasculature. In addition to 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 formation (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 was not induced by platelets from P-selectin(-/-) mice. Moreover, NETosis was also promoted by P-selectin-immunoglobulin fusion protein but not by control immunoglobulin. We isolated neutrophils from mice engineered to overproduce soluble P-selectin (P-selectin(ΔCT/ΔCT) 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 formation after stimulation with platelet activating factor, ionomycin, or phorbol 12-myristate 13-acetate was significantly enhanced, indicating that the P-selectin(ΔCT/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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / physiology
  • Extracellular Traps / drug effects
  • Extracellular Traps / genetics*
  • Extracellular Traps / metabolism
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • P-Selectin / genetics
  • P-Selectin / pharmacology
  • P-Selectin / physiology*
  • Platelet Activation / genetics
  • Recombinant Fusion Proteins / pharmacology
  • Thrombosis / genetics*
  • Thrombosis / pathology
  • Vasculitis / genetics*
  • Vasculitis / pathology


  • P-Selectin
  • Recombinant Fusion Proteins