Impact of CD14 on Reactive Oxygen Species Production from Human Leukocytes Primed by Escherichia coli Lipopolysaccharides

  • Oxid Med Cell Longev. 2019 Mar 3:2019:6043245. doi: 10.1155/2019/6043245.
Dmitry S Kabanov  1 ,  Olga Yu Vwedenskaya  2 ,  Marina A Fokina  2 ,  Elena M Morozova  2 ,  Sergey V Grachev  1  2 ,  Isabella R Prokhorenko  1
Affiliations
  • 1. Department of Molecular Biomedicine, Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", Pushchino 142290, Russia.
  • 2. Department of Pathology of the Institute of Pharmacy, SBAE I. M. Sechenov's First Moscow State Medical University of Russian Healthcare Ministry, Moscow 119811, Russia.
PMID: 30944694 DOI: 10.1155/2019/6043245
Abstract

Lipopolysaccharides (LPS) from Gram-negative bacteria prime human polymorphonuclear neutrophils (PMNs) via multicomponent receptor cluster including CD14 and MD-2·TLR4 for the enhanced release of reactive oxygen species (ROS) were triggered by Bacterial derived peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). In this study, we investigated the impact of CD14 on LPS-induced priming of human PMNs for fMLP-triggered ROS generation (respiratory or oxidative) burst. Monoclonal Antibodies against human CD14 (mAbs) as well as isotype-matched IgG2A did not influence significantly fMLP-triggered ROS production from LPS-unprimed PMNs. Anti-CD14 mAbs (clone UCHM-1) attenuated LPS-induced priming of PMNs as it had been mirrored by fMLP-triggered decrease of ROS production. Similar priming activity of S-LPS or Re-LPS from Escherichia coli for fMLP-triggered ROS release from PMNs was found. Obtained results suggest that glycosylphosphatidylinositol-anchored CD14 is the key player in LPS-induced PMN priming for fMLP-triggered ROS production. We believe that blockade of CD14 on the cell surface and clinical use of anti-CD14 mAbs or their Fab fragments may diminish the production of ROS and improve outcomes during cardiovascular diseases manifested by LPS-induced inflammation.

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