title: Neutrophils exhibit differential requirements for homing molecules in their lymphatic and blood trafficking into draining lymph nodes.
abstract: Although much is described about the molecules involved in neutrophil migration from circulation into tissues, less is known about the molecular mechanisms that regulate neutrophil entry into lymph nodes (LNs) draining a local inflammatory site. In this study, we investigated neutrophil migration toward LNs in a context of inflammation induced by immunization of BALB/c mice with OVA emulsified in CFA. We demonstrated that neutrophils can enter LNs of OVA/CFA-immunized mice not only via lymphatic vessels but also from blood, across high endothelial venules. By adoptive transfer experiments, we showed that this influx was dependent on an inflammatory-state condition and previous neutrophil stimulation with OVA/anti-OVA immune complexes. Importantly, we have demonstrated that, in the migratory pattern to LNs, neutrophils used L-selectin and P-selectin glycoprotein ligand-1, macrophage-1 Ag and LFA-1 integrins, and CXCR4 to get access across high endothelial venules, whereas macrophage-1 Ag, LFA-1, and CXCR4 were involved in their trafficking through afferent lymphatics. Strikingly, we found that stimulation with immune complexes significantly upregulated the expression of sphingosine-1-phosphate receptor 4 on neutrophils, and that treatment with the sphingosine-1-phosphate agonist FTY720 altered neutrophil LN-homing ability. These findings summarized in this article disclose the molecular pattern that controls neutrophil recruitment to LNs.
authors.affiliation: Centro de Investigación en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científica y Técnicas, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, X5000HUA, Argentina.
authors.forename: Carolina V
authors.initials: CV
authors.lastname: Gorlino
authors.affiliation: Centro de Investigación en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científica y Técnicas, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, X5000HUA, Argentina.
authors.forename: Romina P
authors.initials: RP
authors.lastname: Ranocchia
authors.affiliation: Centro de Investigación en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científica y Técnicas, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, X5000HUA, Argentina.
authors.forename: María F
authors.initials: MF
authors.lastname: Harman
authors.affiliation: Centro de Investigación en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científica y Técnicas, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, X5000HUA, Argentina.
authors.forename: Iris A
authors.initials: IA
authors.lastname: García
authors.affiliation: Centro de Investigación en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científica y Técnicas, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, X5000HUA, Argentina.
authors.forename: María I
authors.initials: MI
authors.lastname: Crespo
authors.affiliation: Centro de Investigación en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científica y Técnicas, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, X5000HUA, Argentina.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Morón
authors.affiliation: Centro de Investigación en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científica y Técnicas, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, X5000HUA, Argentina.
authors.forename: Belkys A
authors.initials: BA
authors.lastname: Maletto
authors.affiliation: Centro de Investigación en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científica y Técnicas, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, X5000HUA, Argentina cpistore@fcq.unc.edu.ar.
authors.forename: María C
authors.initials: MC
authors.lastname: Pistoresi-Palencia
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D005260:Female; D000068876:Fingolimod Hydrochloride; D007154:Immune System Diseases / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology; D019041:L-Selectin / Q000276:immunology; D007960:Leukocyte Disorders / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D042601:Lymphatic Vessels / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008246:Lysophospholipids / Q000819:agonists; D016177:Macrophage-1 Antigen / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology* / Q000637:transplantation; D019007:P-Selectin / Q000276:immunology; D011409:Propylene Glycols / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000276:immunology; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000819:agonists / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000936:Antigen-Antibody Complex; C514936:CXCR4 protein, mouse; D007166:Immunosuppressive Agents; D016169:Lymphocyte Function-Associated Antigen-1; D008246:Lysophospholipids; D016177:Macrophage-1 Antigen; D019007:P-Selectin; D011409:Propylene Glycols; D019718:Receptors, CXCR4; D049349:Receptors, Lysosphingolipid; D019041:L-Selectin; C060506:sphingosine 1-phosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine