Abstract
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.—Palladino, E. N. D., L. A. Katunga, G. R. Kolar, and D. A. Ford. 2-Chlorofatty acids: Lipid mediators of neutrophil extracellular trap formation.
Recommended Citation
E. N. Palladino et al., "2-Chlorofatty Acids: Lipid Mediators Of Neutrophil Extracellular Trap Formation," Journal of Lipid Research, vol. 59, no. 8, pp. 1424 - 1432, Elsevier; American Society for Biochemistry and Molecular Biology, Jan 2018.
The definitive version is available at https://doi.org/10.1194/jlr.M084731
Department(s)
Biological Sciences
Publication Status
Open Access
Keywords and Phrases
Cell signaling; Fatty acids; Myeloperoxidase; Neutrophils; Oxidized lipids; Plasmalogens
International Standard Serial Number (ISSN)
1539-7262; 0022-2275
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2025 Elsevier; American Society for Biochemistry and Molecular Biology, All rights reserved.
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution 4.0 License.
Publication Date
01 Jan 2018
PubMed ID
29739865
Comments
National Institutes of Health, Grant R01GM115553