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

P-selectin promotes neutrophil extracellular trap formation in mice.

Author information

1
Laboratory of Experimental Thrombosis, Institute of Experimental Medicine, National Scientific and Technical Research Council, National Academy of Medicine, Buenos Aires, Argentina; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA;
2
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA; Department of Pediatrics, and Immunology Graduate Program, Division of Medical Sciences, Harvard Medical School, Boston, MA; and.
3
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA; Department of Pediatrics, and.
4
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA;
5
Laboratory of Experimental Thrombosis, Institute of Experimental Medicine, National Scientific and Technical Research Council, National Academy of Medicine, Buenos Aires, Argentina;
6
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA; Department of Pediatrics, and Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA.

Abstract

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.

Comment in

PMID:
25979951
PMCID:
PMC4497964
DOI:
10.1182/blood-2015-01-624023
[Indexed for MEDLINE]
Free PMC Article

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