Original Article

Lipids

, Volume 49, Issue 1, pp 49-57

First online:

Protectin DX, a Double Lipoxygenase Product of DHA, Inhibits Both ROS Production in Human Neutrophils and Cyclooxygenase Activities

  • Miao LiuAffiliated withUMR 1060 Inserm (CarMeN), IMBL/INSA-Lyon, Université de Lyon
  • , Tarek BoussettaAffiliated withInserm, UMR 773, CRB3, Faculté de Médecine, Université Paris 7 Denis Diderot
  • , Karama Makni-MaalejAffiliated withInserm, UMR 773, CRB3, Faculté de Médecine, Université Paris 7 Denis Diderot
  • , Michèle FayAffiliated withInserm, UMR 773, CRB3, Faculté de Médecine, Université Paris 7 Denis Diderot
  • , Fathi DrissAffiliated withInserm, UMR 773, CRB3, Faculté de Médecine, Université Paris 7 Denis Diderot
  • , Jamel El-BennaAffiliated withInserm, UMR 773, CRB3, Faculté de Médecine, Université Paris 7 Denis Diderot
  • , Michel LagardeAffiliated withUMR 1060 Inserm (CarMeN), IMBL/INSA-Lyon, Université de Lyon
  • , Michel GuichardantAffiliated withUMR 1060 Inserm (CarMeN), IMBL/INSA-Lyon, Université de Lyon Email author 

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Abstract

Neutrophils play a major role in inflammation by releasing large amounts of reactive oxygen species (ROS) produced by NADPH oxidase (NOX) and myeloperoxidase (MPO). This ROS overproduction is mediated by phosphorylation of the NOX subunits in an uncontrolled manner. Therefore, targeting neutrophil subunits would represent a promising strategy to moderate NOX activity, lower ROS, and other inflammatory agents, such as cytokines and leukotrienes, produced by neutrophils. For this purpose, we investigated the effects of protectin DX (PDX)—a docosahexaenoic acid di-hydroxylated product which inhibits blood platelet aggregation—on neutrophil activation in vitro. We found that PDX decreases ROS production, inhibits NOX activation and MPO release from neutrophils. We also confirm, that PDX is an anti-aggregatory and anti-inflammatory agent by inhibiting both cyclooxygenase-1 and -2 (COX-1 and COX-2, E.C. 1.14.99.1) as well as COX-2 in lipopolysaccharides-treated human neutrophils. However, PDX has no effect on the 5-lipoxygenase pathway that produces the chemotactic agent leukotriene B4 (LTB4). Taken together, our results suggest that PDX could be a protective agent against neutrophil invasion in chronic inflammatory diseases.

Keywords

Human neutrophils Inflammation Protectin DX NADPH oxidase ROS-derived oxidative stress