Neutrophils exhibit differential requirements for homing molecules in their lymphatic and blood trafficking into draining lymph nodes

CAROLINA GORLINO; ROMINA P. RANOCCHIA; FLORENCIA HARMAN; IRIS GARCÍA; MARÍA I CRESPO; MORON VG; BELKYS A. MALETTO; MARÍA C PISTORESI- PALENCIA.

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Lugar: Bethesda; Año: 2014 vol. 193 p. 1966 - 1974

0022-1767

Although much is described about the molecules involved in neutrophil migration fromcirculation into tissues, less is known about the molecular mechanisms that regulateneutrophil entry into lymph nodes (LNs) draining a local inflammatory site. Here weinvestigated neutrophil migration towards LNs in a context of inflammation induced byimmunization of BALB/c mice with ovalbumin (OVA) emulsified in CompleteFreund?s Adjuvant (CFA). We demonstrated that neutrophils can enter LNs ofOVA/CFA-immunized mice not only via lymphatic vessels but also from blood, acrosshigh endothelial venules (HEVs). By adoptive transfer experiments, we showed that thisinflux was dependent on an inflammatory-state condition and previous neutrophilstimulation with OVA/anti-OVA immune complexes. Importantly, we havedemonstrated that, in the migratory pattern to LNs, neutrophils used L-selectin andPSGL-1, Mac-1 and LFA-1 integrins and CXCR4 to get access across HEVs, whileMac-1, LFA-1 and CXCR4 were involved in their trafficking through afferentlymphatics. Strikingly, we found that stimulation with ICs significantly upregulated theexpression of sphingosine-1-phosphate receptor (S1PR) 4 on neutrophils and thattreatment with the S1PR-agonist FTY720 altered neutrophil LN-homing ability. Thesefindings summarized here disclose the molecular pattern that controls neutrophilrecruitment to LNs.