Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 43, Issue 12, Pages 3306-3313Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.201343441
Keywords
Macrophage activation; Peritonitis; Resolution of inflammation; Sphingolipids; Zymosan
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Funding
- Sander Foundation [2013.036.01]
- DFG [SFB 1039]
- Else Kroner-Fresenius Foundation (EKFS) Researcg Training Group Translational Research Innovation-Pharma (TRIP)
- Paul und Ursula Klein-Stiftung
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The lipid sphingosine-1-phosphate (S1P) is a chemokine for a variety of immune cells including lymphocytes and monocytes. Migration toward S1P is determined by the S1P receptor expression profile, with S1PR1/3 (where S1PR is S1P receptor) stimulating and S1PR2 attenuating migration. However, the impact and physiological significance of S1P-induced migration of macrophages is largely unclear. We observed that alternative activation of human macrophages, by IL-4 or apoptotic cells (ACs), enhanced S1PR1 expression. Moreover, ACs provoked macrophage migration toward S1P in an S1PR1-dependent manner as confirmed by pharmacological receptor inhibition and S1PR1-deficient murine macrophages. In a mouse model of resolving peritoneal inflammation, F4/80-driven deletion of S1PR1 reduced postinflammatory macrophage emigration from inflammatory sites. S1PR1 expression on macrophages might, therefore, be relevant for restoring tissue homeostasis during the resolution of inflammation.
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