期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 82, 期 5, 页码 1193-1200出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.0407221
关键词
sphingosine-1-phosphate; GPCR; chemoattractant; bioactive lipid; inflammation
资金
- NCI NIH HHS [R21 CA109291] Funding Source: Medline
- NCRR NIH HHS [C06 RR018928] Funding Source: Medline
- NIDDK NIH HHS [R01 DK056084] Funding Source: Medline
- NIMH NIH HHS [MH51699] Funding Source: Medline
- NINDS NIH HHS [NS048478] Funding Source: Medline
Increasing evidence supports roles for lipids in the biology of immune cells. In particular, bioactive lipids such as sphingosine-1-phosphate (SIP) 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 SIP 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, aid 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 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.
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