Document Type



Life Sciences | Medicine and Health Sciences


Macrophage recruitment to sites of inflammation is an essential step in host defense. However, the mechanisms preventing excessive accumulation of macrophages remain relatively unknown. The lysophospholipid sphingosine 1-phosphate (S1P) promotes T and B cell egress from lymphoid organs by acting on S1P receptor 1 (S1P1R). More recently, S1P5R was shown to regulate NK cell mobilization during inflammation, raising the possibility that S1P regulates the trafficking of other leukocyte lineages. In this study, we show that S1P2R inhibits macrophage migration in vitro and that S1P2R-deficient mice have enhanced macrophage recruitment during thioglycollate peritonitis. We identify the signaling mechanisms used by S1P2R in macrophages, involving the second messenger cAMP and inhibition of Akt phosphorylation. In addition, we show that the phosphoinositide phosphatase and tensin homolog deleted on chromosome 10, which has been suggested to mediate S1P2R effects in other cell types, does not mediate S1P2R inhibition in macrophages. Our results suggest that S1P serves as a negative regulator of macrophage recruitment by inhibiting migration in these cells and identify an additional facet to the regulation of leukocyte trafficking by S1P.


J Immunol. Author manuscript; available in PMC 2011 March 31.

PMCID: PMC3068864

Published in final edited form as: J Immunol. 2010 February 1; 184(3): 1475–1483. Published online 2009 December 30. doi: 10.4049/jimmunol.0901586.