Sphingosylphosphorylcholine activates dendritic cells, stimulating the production of interleukin-12.
Compared with other lysophospholipid mediators such as sphingosine-1-phosphate and lysophosphatidic acid, little is known about the physiological significance of the related bioactive lysosphingolipid sphingosylphosphorylcholine (SPC), which is present in high-density lipoprotein particles. The present study was undertaken to evaluate the effect of SPC on human immature dendritic cells (DCs). Reverse transcription-polymerase chain reaction and flow cytometry assays revealed that DCs express two putative receptors for SPC, ovarian cancer G-protein-coupled receptor 1 and G-protein-coupled receptor 4. Exposure to SPC induced a rapid and transient increase in intracellular free calcium concentrations but did not stimulate endocytosis or chemotaxis of DCs. SPC increased the expression of HLA-DR, CD86 and CD83 and improved the T-cell priming ability of DCs, as well as the ability of DCs to stimulate the production of interferon-gamma by allogeneic peripheral blood mononuclear cells during the mixed lymphocyte reaction. Consistent with these results, we also observed that SPC stimulated the production of interleukin (IL)-12 and IL-18 by DCs. Taken together, our results support the notion that the accumulation of SPC in peripheral tissues during the course of inflammatory processes may favour the development of T helper type 1 immunity.
Ceballos
Ana
A
National Reference Center for AIDS, Department of Microbiology, Buenos Aires University School of Medicine, Buenos Aires, Argentina.
Sabatté
Juan
J
Nahmod
Karen
K
Martínez
Diego
D
Salamone
Gabriela
G
Vermeulen
Mónica
M
Maggini
Julián
J
Salomón
Horacio
H
Geffner
Jorge
J
D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002633:Chemotaxis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000276:immunology; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000276:immunology; D000097802:CD83 Antigen
D015703:Antigens, CD; D051940:B7-2 Antigen; D002118:Calcium; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D007371:Interferon-gamma; D018664:Interleukin-12; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D010767:Phosphorylcholine; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D000097802:CD83 Antigen; C005356:sphingosine phosphorylcholine