Proceedings of the National Academy of Sciences - PNAS, 2014-11, Vol.111 (46), p.16526-16531
2014
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- Autor(en) / Beteiligte
- Titel
- Maresin 1 biosynthesis during platelet–neutrophil interactions is organ-protective
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2014-11, Vol.111 (46), p.16526-16531
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2014
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Unregulated acute inflammation can lead to collateral tissue injury in vital organs, such as the lung during the acute respiratory distress syndrome. In response to tissue injury, circulating platelet–neutrophil aggregates form to augment neutrophil tissue entry. These early cellular events in acute inflammation are pivotal to timely resolution by mechanisms that remain to be elucidated. Here, we identified a previously undescribed biosynthetic route during human platelet–neutrophil interactions for the proresolving mediator maresin 1 (MaR1; 7R,14S-dihydroxy-docosa-4Z,8E,10E,12Z,16Z,19Z-hexaenoic acid). Docosahexaenoic acid was converted by platelet 12-lipoxygenase to 13S,14S-epoxy-maresin, which was further transformed by neutrophils to MaR1. In a murine model of acute respiratory distress syndrome, lipid mediator metabololipidomics uncovered MaR1 generation in vivo in a temporally regulated manner. Early MaR1 production was dependent on platelet–neutrophil interactions, and intravascular MaR1 was organ-protective, leading to decreased lung neutrophils, edema, tissue hypoxia, and prophlogistic mediators. Together, these findings identify a transcellular route for intravascular maresin 1 biosynthesis via platelet–neutrophil interactions that regulates the extent of lung inflammation. Significance Neutrophil accumulation is fundamental to acute inflammation. In response to tissue injury, circulating neutrophil–platelet aggregates (N-PAs) form for secondary capture. Counterregulation of acute inflammatory processes by specialized proresolving mediators is essential to mitigate collateral injury to healthy bystander tissue. Here, we identified a biosynthetic route in human platelets for the proresolving mediator maresin 1 (MaR1) that is amplified during platelet–neutrophil interactions. In a self-resolving murine model of acute lung injury, N-PAs rapidly formed and a MaR1 counterregulatory circuit was engaged to restrain N-PAs and acute inflammation and restore homeostasis of the injured lung.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1407123111Titel-ID: cdi_jstor_primary_43190256
- Format
- –
- Schlagworte
- Adult respiratory distress syndrome, Animals, Arachidonate 12-Lipoxygenase - metabolism, Biological Sciences, Biosynthesis, Blood, Blood platelets, Blood Platelets - drug effects, Blood Platelets - metabolism, Bronchoalveolar Lavage Fluid - cytology, Cell Hypoxia, Chemotaxis, Leukocyte, Disease Models, Animal, Docosahexaenoic Acids - biosynthesis, Docosahexaenoic Acids - metabolism, Docosahexaenoic Acids - pharmacology, Docosahexaenoic Acids - physiology, Docosahexaenoic Acids - therapeutic use, Heterografts, Humans, Hydrochloric Acid - toxicity, Hypoxia, Inflammation, Inflammation - metabolism, Inflammation - pathology, Lung - drug effects, Lung - metabolism, Lung - pathology, Lungs, Macrophages, Male, Marl, Metabolomics, Mice, Mice, Inbred BALB C, Molecular Structure, Neutrophils, Neutrophils - metabolism, Physical trauma, Platelet Activating Factor - pharmacology, Platelet Transfusion, Platelets, Recombinant Proteins - metabolism, Respiratory distress syndrome, Respiratory Distress Syndrome, Adult - chemically induced, Respiratory Distress Syndrome, Adult - drug therapy, Respiratory Distress Syndrome, Adult - metabolism, Respiratory Distress Syndrome, Adult - pathology, Thrombin - pharmacology, Tissues