Role of sphingosine-1-phosphate in neutrophil trafficking to lymph nodes in an immune inflammation model

GORLINO, C.; RANOCCHIA, R.; HARMAN, M.F.; MORÓN, G.; MALETTO, B.; PISTORESI, MC.

Buenos Aires

Congreso; First French-Argentine Immunology Congress y LVIII Reunión Anual de la Sociedad Argentina de Inmunología; 2010

SAI

We previously showed that when OVA-FITC was injected into the footpad of OVA/CFA immunized mice, the main OVA-FITC+ cells recruited in draining popliteal lymph nodes were neutrophils and this influx was dependent on an antigen-specific response. Moreover, we showed that neutrophils entered into lymph nodes through afferent lymphatics and blood. On the basis of these findings, we investigated if the phospholipid sphingosine 1-phosphate (S1P) is involved in this migration. Treatment with the S1P receptor agonist FTY720 bloqued neutrophil influx in OVA/CFA immunized mice (43±3 vs 9±4; p=0.02) but not its recruitment to the skin (23±2 vs 16±3; p=0.19). To further characterize the role of S1P in neutrophil trafficking from skin (by lymph vessels) or from blood into lymph nodes, we performed adoptive transfer experiments. Bone marrow neutrophils incubated with immune complexes (anti-OVA rabbit sera plus OVA) were labeled with DiIC(18)-DS and injected intravenously or subcutaneously into the footpads of FTY720 treated OVA/CFA-immunized mice. FTY720 treatment caused impaired migration from footpad to popliteal lymph nodes (0.44±0.08 vs 0.21±0.04; p