TY - JOUR T1 - The role of leptin in pulmonary neutrophilia during murine acute lung injury JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p4592 AU - N.D. Ubags AU - J.H. Vernooy AU - E. Burg AU - C. Lenox AU - L.L. Kordonowy AU - J. Petty AU - K. DiPalma AU - E.F. Wouters AU - B.T. Suratt Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p4592.abstract N2 - Rationale: One of the hallmarks of Acute Lung Injury (ALI) is the extensive recruitment of neutrophils to the lung. Recent evidence shows that leptin expression is increased in the injured human lung, and is known to have diverse effects on leucocytes. We hypothesized that leptin contributes directly to neutrophil recruitment in the lung during ALI.Methods: C57/Bl6 wild type (WT) mice were examined in a lipopolysaccharide (LPS) model of lung injury with or without oropharyngeal aspiration of recombinant leptin. We measured bronchoalveolar lavage (BAL) neutrophilia, leptin concentrations and inflammatory cytokine levels at 24 hours after injury. In addition, the effects of LPS induced lung injury were examined in leptin resistant (db/db) obese and Diet Induced Obese (DIO) mice and their lean controls. Lastly, we examined chemotaxis to leptin in neutrophils isolated from lean and obese uninjured mice.Results: BAL leptin levels were significantly increased in injured WT mice (1324 pg/ml ± 320) relative to their saline-treated controls (96 pg/ml ± 74) 24 hours after LPS exposure. Recombinant leptin augmented airspace neutrophilia after LPS exposure in WT mice, yet inflammatory cytokine levels in BAL remained unchanged. In addition, we observed attenuation in BAL neutrophilia in both db/db and DIO obese mice compared to their lean controls. Lastly, neutrophils were found to migrate to leptin in vitro, and obesity blunted this response.Conclusion: Our findings indicate that leptin plays a role in neutrophil recruitment to the lung during ALI. This appears to occur in part via leptin-induced neutrophil chemotaxis, which is diminished in obesity. ER -