LPA3 receptor mediates chemotaxis of immature murine dendritic cells to unsaturated lysophosphatidic acid (LPA)

Liana C. Chan, Wendy Peters, Yan Xu, Jerold Chun, Robert V. Farese, Sylvaine Cases

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Increasing evidence supports roles for lipids in the biology of immune cells. In particular, bioactive lipids such as sphingosine-1-phosphate (S1P) bind to cognate G protein-coupled receptors (GPCRs) and modulate leukocyte trafficking and homeostasis. Lysophosphatidic acid (LPA) represents a family of bioactive lipids, which differ in the length and degree of saturation of the fatty acyl chain. LPA is structurally related to S1P and exerts cellular effects by binding to five known GPCRs (LPA1-5). Its function in the immune system is less clear, although it was shown to induce chemotaxis of human dendritic cells (DCs) and activated T cells. In this study, we show that LPA can induce chemotaxis of immature but not mature mouse DCs and that only unsaturated and not saturated LPA species are efficient chemoattractants. However, both LPA species do not alter DC maturation or chemotaxis to other chemokines. The loss of DC migration capability correlated with the down-regulation of expression of the receptors LPA3 and LPA 5, and expression of LPA1, LPA2, and LPA 4 did not change. A LPA3 antagonist reduced immature DC migration to LPA by 70%, suggesting that LPA3 mediates immature DC chemotaxis to unsaturated species of LPA. Furthermore, isolated, immature DCs from mice lacking LPA3 exhibited a 50% reduction in migration to LPA. In summary, our results indicate that immature mouse DCs migrate preferentially in response to unsaturated LPA and that LPA3 is important in this response.

Original languageEnglish (US)
Pages (from-to)1193-1200
Number of pages8
JournalJournal of Leukocyte Biology
Volume82
Issue number5
DOIs
StatePublished - Nov 1 2007

Keywords

  • Bioactive lipid
  • Chemoattractant
  • GPCR
  • Inflammation
  • Sphingosine-1-phosphate

ASJC Scopus subject areas

  • Cell Biology

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