Sphingosylphosphorylcholine activates dendritic cells, stimulating the production of interleukin-12

• Published in: Immunology 2007-07, Vol.121 (3), p.328-336
• Main Authors: Ceballos, Ana, Sabatté, Juan, Nahmod, Karen, Martínez, Diego, Salamone, Gabriela, Vermeulen, Mónica, Maggini, Julián, Salomón, Horacio, Geffner, Jorge
• Format: Article
• Language: English
• Subjects: Antigens, CD - metabolism; B7-2 Antigen - metabolism; Calcium - metabolism; CD83 Antigen; Cells, Cultured; Chemotaxis - immunology; dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Endocytosis - immunology; HLA-DR Antigens - metabolism; Humans; Immunoglobulins - metabolism; Interferon-gamma - biosynthesis; interleukin-12; Interleukin-12 - biosynthesis; interleukin-18; Interleukin-18 - biosynthesis; Lymphocyte Culture Test, Mixed; Membrane Glycoproteins - metabolism; Original; Phosphorylcholine - analogs & derivatives; Phosphorylcholine - immunology; Receptors, Lysosphingolipid - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; Sphingosine - analogs & derivatives; Sphingosine - immunology; sphingosylphosphorylcholine
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2007.02578.x

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-γ 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.