2-Chlorofatty acids: lipid mediators of neutrophil extracellular trap formation.

Autor:	Palladino END; Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104.; Center for Cardiovascular Research Saint Louis University School of Medicine, St. Louis, MO 63104., Katunga LA; Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104.; Center for Cardiovascular Research Saint Louis University School of Medicine, St. Louis, MO 63104., Kolar GR; Pathology Department Saint Louis University School of Medicine, St. Louis, MO 63104.; Research Microscopy and Histology Core, Saint Louis University School of Medicine, St. Louis, MO 63104., Ford DA; Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104 david.ford@health.slu.edu.; Center for Cardiovascular Research Saint Louis University School of Medicine, St. Louis, MO 63104.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2018 Aug; Vol. 59 (8), pp. 1424-1432. Date of Electronic Publication: 2018 May 08.
DOI:	10.1194/jlr.M084731
Abstrakt:	Neutrophils form neutrophil extracellular traps (NETs), which have been implicated in microcirculatory plugging. NET formation (NETosis) involves the fusion of granule and nuclear contents, which are then released in the extracellular space. Myeloperoxidase (MPO) plays a major role in NETosis leading to the dissociation of DNA from histones. During neutrophil activation, MPO is released and activated to convert hydrogen peroxide and chloride to hypochlorous acid (HOCl). HOCl targets plasmalogens leading to the production of the chlorinated lipids, 2-chlorofatty aldehyde and 2-chlorofatty acid (2-ClFA). Here, we tested the hypothesis that 2-ClFAs are important lipid mediators of NETosis. Human neutrophils treated with physiological levels of 2-ClFAs formed NETs, characterized by MPO association with DNA and neutrophil elastase (NE) redistribution to the perinuclear area. 2-ClFA-induced NETs reduced Escerichia coli colony forming units. 2-ClFA-induced NETosis is calcium- and protein arginine deiminase 4-dependent. Interestingly, unlike PMA, 2-ClFA initiates the NETosis process without neutrophil activation and degranulation. Furthermore, 2-ClFA elicits NETosis in bone-marrow derived neutrophils from MPO-deficient mice. Taken together, these findings suggest 2-ClFA as an MPO product that triggers the NETosis pathway following neutrophil activation. (Copyright © 2018 Palladino et al.)
Databáze:	MEDLINE
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