Leptin Mediates In Vivo Neutrophil Migration: Involvement of Tumor Necrosis Factor-Alpha and CXCL1

Souza-Almeida, Glaucia; D'Avila, Heloisa; Almeida, Patricia E.; Luna-Gomes, Tatiana; Liechocki, Sally; Walzog, Barbara; Hepper, Ingrid; Castro-Faria-Neto, Hugo Caire; Bozza, Patricia T.; Bandeira-Melo, Christianne und Maya-Monteiro, Clarissa M. (2018): Leptin Mediates In Vivo Neutrophil Migration: Involvement of Tumor Necrosis Factor-Alpha and CXCL1. In: Frontiers in Immunology, Bd. 9, 111

Abstract

Leptin directly activates macrophages and lymphocytes, but the role of leptin in neutrophil activation and migration is still controversial. Here, we investigate the in vivo mechanisms of neutrophil migration induced by leptin. The intraperitoneal injection of leptin (1 mg/kg) induces a time- and concentration dependent neutrophil influx. We did not observe the enhancement of lipid bodies/droplets in neutrophils, after leptin treatment, as we had observed previously in peritoneal macrophages. The participation of leukotriene B-4 (LTB4) in neutrophil recruitment triggered by leptin was investigated using different strategies. Leptin induced neutrophil recruitment occurs both in the absence of 5-lipoxygenase activity in 5-lipoxygenase (5-LO)(-/-) mice and after the administration of either 5-LO inhibitor (Zileuton) or the LTR4 receptor antagonist (U-75302). Moreover, no direct induction of LIB, by leptin could be observed. Neutrophil influx could not be prevented by the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, contrasting with the leptin-induced signaling for lipid body formation in macrophage that is mTOR-dependent. Leptin administration led to tumor necrosis factor-alpha (TNR alpha) production by the peritoneal cells both in vivo and in vitro. In addition, neutrophil recruitment was inhibited in tumor necrosis factor receptor 1 (INFR1(-/-)) mice, indicating a role for TNF in leptin-induced neutrophil recruitment to the peritoneal cavity. Leptin-induced neutrophil influx was PI3K gamma-dependent, as it was absent in PI3K gamma(-/-) mice. Accordingly, leptin induced the peritoneal cells to produce CXCL1, both in vivo and in vitro, and the neutrophil influx was ablated after using an antibody against CXCL1. Our results establish TNR alpha/TNFR1- and CXCL1 dependent signaling as important pathways for leptin-induced neutrophil migration in vivo.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1664-3224
• Sprache: Englisch