Resolvin E1 and protectin D1 activate inflammation-resolution programmes

Jan M. Schwab, Nan Chiang, Makoto Arita, Charles N. Serhan

Research output: Contribution to journalArticle

768 Citations (Scopus)

Abstract

Resolution of acute inflammation is an active process essential for appropriate host responses, tissue protection and the return to homeostasis. During resolution, specific omega-3 polyunsaturated fatty-acid-derived mediators are generated within resolving exudates, including resolvin E1 (RvE1) and protectin D1 (PD1). It is thus important to pinpoint specific actions of RvE1 and PD1 in regulating tissue resolution. Here we report that RvE1 and PD1 in nanogram quantities promote phagocyte removal during acute inflammation by regulating leukocyte infiltration, increasing macrophage ingestion of apoptotic polymorphonuclear neutrophils in vivo and in vitro, and enhancing the appearance of phagocytes carrying engulfed zymosan in lymph nodes and spleen. In this tissue terrain, inhibition of either cyclooxygenase or lipoxygenases - pivotal enzymes in the temporal generation of both pro-inflammatory and pro-resolving mediators - caused a 'resolution deficit' that was rescued by RvE1, PD1 or aspirin-triggered lipoxin A4 analogue. Also, new resolution routes were identified that involve phagocytes traversing perinodal adipose tissues and non-apoptotic polymorphonuclear neutrophils carrying engulfed zymosan to lymph nodes. Together, these results identify new active components for postexudate resolution traffic, and demonstrate that RvE1 and PD1 are potent agonists for resolution of inflamed tissues.

Original languageEnglish
Pages (from-to)869-874
Number of pages6
JournalNature
Volume447
Issue number7146
DOIs
Publication statusPublished - 2007 Jun 14
Externally publishedYes

ASJC Scopus subject areas

  • General

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