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* Department of Experimental Dermatology, University of Freiburg, Freiburg, Germany;
Laboratory of Immunology, Istituto Dermopatico dell’Immacolata, Institute for Cancer Research and Treatment, Rome, Italy; and
Section of General Pathology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy
Lysophosphatidic acid (LPA) is a bioactive lipid mediator which is
generated by secretory phospholipase A2. In this study, we
studied the biological activity of LPA on human dendritic cells (DCs),
which are specialized APCs characterized by their ability to migrate
into target sites and secondary lymphoid organs to process Ags and
activate naive T cells. We show that immature and mature DCs express
the mRNA for different LPA receptors such as endothelial
differentiation gene (EDG)-2, EDG-4, and EDG-7. In immature DCs, LPA
stimulated pertussis toxin-sensitive Ca2+ increase, actin
polymerization, and chemotaxis. During the maturation process, DCs lost
their ability to respond toward LPA with Ca2+ transients,
actin polymerization, and chemotaxis. However, LPA inhibited in a
pertussis toxin-insensitive manner the secretion of IL-12 and TNF
as
well as enhanced secretion of IL-10 from mature DCs. Moreover, LPA did
not affect the endocytic or phagocytic capacities and the surface
phenotype of DCs, although it increased the allostimulatory function of
mature DC and inhibited their capacity to induce Th1 differentiation.
In summary, our study implicates that LPA might regulate the
trafficking, cytokine production, and T cell-activating functions of
DCs.
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