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

• Published in: The Journal of immunology (1950) Vol. 193; no. 4; pp. 1966 - 1974
• Main Authors: Gorlino, Carolina V, Ranocchia, Romina P, Harman, María F, García, Iris A, Crespo, María I, Morón, Gabriel, Maletto, Belkys A, Pistoresi-Palencia, María C
• Format: Journal Article
• Language: English
• Published: United States 15.08.2014
• Subjects: Adoptive Transfer; Animals; Antigen-Antibody Complex - immunology; Cell Movement - immunology; Female; Fingolimod Hydrochloride; Immune System Diseases - immunology; Immunosuppressive Agents - pharmacology; Inflammation - immunology; L-Selectin - immunology; Leukocyte Disorders - immunology; Lymph Nodes - cytology; Lymph Nodes - immunology; Lymphatic Vessels - immunology; Lymphocyte Function-Associated Antigen-1 - immunology; Lysophospholipids - agonists; Macrophage-1 Antigen - immunology; Mice; Mice, Inbred BALB C; Neutrophils - immunology; Neutrophils - transplantation; P-Selectin - immunology; Propylene Glycols - pharmacology; Receptors, CXCR4 - immunology; Receptors, Lysosphingolipid - metabolism; Sphingosine - agonists; Sphingosine - analogs & derivatives; Sphingosine - pharmacology
• DOI: 10.4049/jimmunol.1301791
• ISSN: 0022-1767

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.