TY - JOUR T1 - Reduced 15-lipoxygenase 2 and lipoxin A<sub>4</sub>/leukotriene B<sub>4</sub> ratio in children with cystic fibrosis JF - European Respiratory Journal JO - Eur Respir J SP - 394 LP - 404 DO - 10.1183/09031936.00106013 VL - 44 IS - 2 AU - Fiona C. Ringholz AU - Paul J. Buchanan AU - Donna T. Clarke AU - Roisin G. Millar AU - Michael McDermott AU - Barry Linnane AU - Brian J. Harvey AU - Paul McNally AU - Valerie Urbach Y1 - 2014/08/01 UR - http://erj.ersjournals.com/content/44/2/394.abstract N2 - Airway disease in cystic fibrosis (CF) is characterised by impaired mucociliary clearance, persistent bacterial infection and neutrophilic inflammation. Lipoxin A4 (LXA4) initiates the active resolution of inflammation and promotes airway surface hydration in CF models. 15-Lipoxygenase (LO) plays a central role in the “class switch” of eicosanoid mediator biosynthesis from leukotrienes to lipoxins, initiating the active resolution of inflammation. We hypothesised that defective eicosanoid mediator class switching contributes to the failure to resolve inflammation in CF lung disease. Using bronchoalveolar lavage (BAL) samples from 46 children with CF and 19 paediatric controls we demonstrate that the ratio of LXA4 to leukotriene B4 (LTB4) is depressed in CF BAL (p&lt;0.01), even in the absence of infection (p&lt;0.001). Furthermore, 15-LO2 transcripts were significantly less abundant in CF BAL samples (p&lt;0.05). In control BAL, there were positive relationships between 15-LO2 transcript abundance and LXA4/LTB4 ratio (p=0.01, r=0.66) and with percentage macrophage composition of the BAL fluid (p&lt;0.001, r=0.82), which were absent in CF. Impoverished 15-LO2 expression and depression of the LXA4/LTB4 ratio are observed in paediatric CF BAL. These observations provide mechanistic insights into the failure to resolve inflammation in the CF lung. Reduced 15-LO2 expression in the lower airways of children with CF, associated with a depressed LXA4/LTB4 ratio http://ow.ly/tzZWa ER -