Abstract
Aim:
To investigate the effects of sphingosylphosphorylcholine (SPC) on human monocyte-derived dendritic cell (DC) chemotaxis.
Methods:
Human DC were generated from peripheral blood monocytes by culturing them with granulocyte macrophage-colony stimulating factor and interleukin-4. The effect of SPC on the DC chemotactic migration was measured by chemotaxis assay. Intracellular signaling event involved in the SPC-induced DC chemotaxis was investigated with several inhibitors for specific kinase. The expression of the SPC receptors was examined by reverse transcription polymerase chain reaction.
Results:
We found that SPC induced chemotactic migration in immature DC (iDC) and mature DC (mDC). In terms of SPC-induced signaling events, mitogen activated protein kinase activation and Akt activation in iDC and mDC were stimulated. SPC-induced chemotaxis was mediated by extracellular signal-regulated protein kinase and phosphoino-sitide-3-kinase, but not by calcium in both iDC and mDC. Although mDC express ovarian cancer G protein-coupled receptor 1, but not G protein-coupled receptor 4, iDC do not express any of these receptors. To examine the involvement of sphin-gosine-1-phosphate (S1P) receptors, we checked the effect of an S1P receptor antagonist (VPC23019) on SPC-induced DC chemotaxis. VPC23019 did not affect SPC-induced DC chemotaxis.
Conclusion:
The results suggest that SPC may play a role in regulating DC trafficking during phagocytosis and the T cell-stimulating phase, and the unique SPC receptor, which is different from S1P receptors, is involved in SPC-induced chemotaxis.
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Project supported by the Korea Science and Engineering Foundation through the Medical Science and Engineering Research Center for Cancer Molecular Therapy at Dong-A University, the Korea Science and Engineering Foundation Grant (No R01-2005-000-10011-02005), and a grant from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (No 02-PJ2-PG1-CH16-0002).
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Lee, Hy., Shin, Eh. & Bae, Ys. Sphingosylphosphorylcholine stimulates human monocyte-derived dendritic cell chemotaxis. Acta Pharmacol Sin 27, 1359–1366 (2006). https://doi.org/10.1111/j.1745-7254.2006.00426.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00426.x