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Chlorinated Lipids Elicit Neutrophil‐Endothelial Interactions in Mesenteric Microcirculation
Author(s) -
Yu Hong,
Wang Meifang,
Wang Derek Z.,
Kalogeris Ted,
Ford David A.,
Ronald Korthuis J.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.679.5
Subject(s) - hypochlorous acid , myeloperoxidase , chemistry , mesenteries , biochemistry , proinflammatory cytokine , reactive oxygen species , inflammation , extravasation , intravital microscopy , immunology , microcirculation , biology , medicine , anatomy
Neutrophils are key early responders to infection, and kill microbes by phagocytosis and oxidant‐mediated mechanisms that involve, in part, myeloperoxidase (MPO). Hypochlorous acid (HOCl) produced by MPO targets plasmalogen phospholipids at vinyl ether bonds to generate 2‐chlorohexadecanal (2‐ClHDA) and 2‐chloropalmitic acid (2‐ClPA). Our previous work showed that levels of 2‐ClPA increased in both plasma and cecum of rats subjected to cecal ligation and puncture (CLP, a model of polymicrobial sepsis) when compared to sham rats. However, it is not clear whether chlorinated lipid species can exert proinflammatory effects including elevated neutrophil‐endothelial interaction, reactive oxygen species (ROS) production and inflammatory markers levels. We have begun to explore this issue by exposing naïve rats to exogenous chlorinated lipids. Mesenteries in four groups of Sprague‐Dawley rats (n=6) were superfused with 10 μM 2‐ClHDA, hexadecanal (HDA), 2‐ClPA and palmitic acid (PA), respectively, and inflammatory responses were measured using intravital microscopy and other assays. Treatment with chlorinated lipids showed significant increases in neutrophil‐endothelial interactions including leukocyte rolling and adhesion as well as ROS production when compared with non‐chlorinated lipids. Tissue MPO levels were also elevated after exposure to chlorinated lipids, while the tissue levels of tumor necrosis factor α (TNFα) were not different when comparing to mesenteries treated with equimolar concentrations of non‐chlorinated lipids. These results show for the first time that chlorinated lipids, which may be formed secondary to the enzymatic action of neutrophilic MPO to produce HOCl in inflammation, elicit neutrophil‐endothelial interactions and other inflammatory response in naïve rats. Support or Funding Information Supported by NIH grant GM‐115553.