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LPA 3 receptor mediates chemotaxis of immature murine dendritic cells to unsaturated lysophosphatidic acid (LPA)
Author(s) -
Chan Liana C.,
Peters Wendy,
Xu Yan,
Chun Jerold,
Farese Robert V.,
Cases Sylvaine
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0407221
Subject(s) - lysophosphatidic acid , chemotaxis , biology , microbiology and biotechnology , receptor , g protein coupled receptor , chemokine , sphingosine , immune system , dendritic cell , signal transduction , biochemistry , immunology
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 (LPA 1–5 ). 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 LPA 3 and LPA 5 , and expression of LPA 1 , LPA 2 , and LPA 4 did not change. A LPA 3 antagonist reduced immature DC migration to LPA by 70%, suggesting that LPA 3 mediates immature DC chemotaxis to unsaturated species of LPA. Furthermore, isolated, immature DCs from mice lacking LPA 3 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 LPA 3 is important in this response.