Apoptotic cells enhance sphingosine-1-phosphate receptor 1 dependent macrophage migration.
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.
Institute of Biochemistry I/ZAFES, Goethe-University Frankfurt, Frankfurt, Germany.
Benjamin
B
Weichand
Nicole
N
Weis
Andreas
A
Weigert
Nina
N
Grossmann
Bodo
B
Levkau
Bernhard
B
Brüne
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008246:Lysophospholipids / Q000235:genetics / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000276:immunology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000276:immunology; D000081025:Sphingosine-1-Phosphate Receptors
C508598:IL4 protein, human; D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; C556330:S1pr1 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors; D015847:Interleukin-4; C060506:sphingosine 1-phosphate; D013110:Sphingosine
Macrophage activation; Peritonitis; Resolution of inflammation; Sphingolipids; Zymosan