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

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

Buenos Aires

Congreso; First French-Argentine Immunology Congress (FAIC)-LVIII Reunión Científica de la Sociedad Argentina de Inmunología; 2010

SOCIEDAD ARGENTINA DE INMUNOLOGIA

We previously demonstrated 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 and that this migration was dependent on the presence of immune complexes as well as on an inflammatory condition. On the basis of these findings, we investigated if the phospholipid sphingosine-1-phosphate (S1P) is involved in this traffic. Treatment with the S1P receptor modulator FTY720 inhibited neutrophil influx in draining popliteal lymph nodes of mice immunized with OVA (43±3% vs 9±4%; p=0.02) but not its recruitment to the site of inflammation (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 reactive lymph nodes, we performed adoptive transfer experiments. Bone marrow neutrophils incubated with immune complexes (anti-OVA rabbit sera plus OVA) were differentially labeled either with DiIC(18)-DS or DiOC(18)-SP and simultaneously injected i.v. and s.c. into the footpads, respectively, of FTY720 treated OVA/CFA-immunized mice. The administration of FTY720 caused impaired migration of transferred neutrophils from footpad to popliteal lymph nodes (0.44±0.08% vs 0.21±0.04%; p