Maresin 1 biosynthesis during platelet-neutrophil interactions is organ-protective

被引：149

作者：

Abdulnour, Raja-Elie E. ^{[1
]}

Dalli, Jesmond ^{[2
,3
]}

Colby, Jennifer K. ^{[1
]}

Krishnamoorthy, Nandini ^{[1
]}

Timmons, Jack Y. ^{[1
]}

Tan, Sook Hwa ^{[1
]}

Colas, Romain A. ^{[2
,3
]}

Petasis, Nicos A. ^{[4
]}

Serhan, Charles N. ^{[2
,3
]}

Levy, Bruce D. ^{[1
,2
,3
]}

机构：

[1] Brigham & Womens Hosp, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Boston, MA 02115 USA

[4] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 46期

基金：

美国国家卫生研究院;

关键词：

maresin; platelet; inflammation; lung; resolution; ACUTE LUNG INJURY; ACUTE-INFLAMMATION; IN-VIVO; RESOLUTION; MICE; AGGREGATION; PNEUMONIA; SEVERITY; ADHESION;

D O I：

10.1073/pnas.1407123111

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：16526 / 16531

页数：6

共 29 条

[21] The Anti-Inflammatory and Proresolving Mediator Resolvin E1 Protects Mice from Bacterial Pneumonia and Acute Lung Injury [J].