The influence of lysophosphatidic acid on the functions of human dendritic cells.
Lysophosphatidic acid (LPA) is a bioactive lipid mediator which is generated by secretory phospholipase A(2). 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 Ca(2+) increase, actin polymerization, and chemotaxis. During the maturation process, DCs lost their ability to respond toward LPA with Ca(2+) transients, actin polymerization, and chemotaxis. However, LPA inhibited in a pertussis toxin-insensitive manner the secretion of IL-12 and TNFalpha 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.
Panther
Elisabeth
E
Department of Experimental Dermatology, University of Freiburg, Hauptstrasse 7, D-79104 Freiburg i.Br., Germany.
Idzko
Marco
M
Corinti
Silvia
S
Ferrari
Davide
D
Herouy
Yared
Y
Mockenhaupt
Maja
M
Dichmann
Stefan
S
Gebicke-Haerter
Peter
P
Di Virgilio
Francesco
F
Girolomoni
Giampiero
G
Norgauer
Johannes
J
D000199:Actins / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D011108:Polymers / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000199:Actins; D000276:Adjuvants, Immunologic; D008246:Lysophospholipids; D011108:Polymers; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12