Leukotriene A4Hydrolase Inhibition Attenuates Allergic Airway Inflammation and Hyperresponsiveness

• DOI: 10.1164/rccm.200807-1158oc
• Publication Date: 2010-01-29T03:45:00Z
• Authors: Navin L. Rao; Jason P. Riley; Homayon Banie; Xiaohua Xue; Binggang Sun; Shelby Crawford; Katherine A. Lundeen; Fuqu Yu; Lars Karlsson; Anne M. Fourie; Paul J. Dunford
• Keywords: Leukotriene B4; Allergic Inflammation; Adoptive Cell Transfer

Allergic asthma is characterized by reversible airway obstruction, lung inflammation, and hyperresponsiveness (AHR). Previous studies using leukotriene B(4) (LTB(4)) receptor 1-deficient mice adoptive transfer experiments have suggested that LTB(4) plays a role in inflammation AHR.In this study, we used A(4) hydrolase (LTA(4)H) inhibitor as pharmacological tool to directly examine the of mast cell-dependent murine model allergic inflammation.We forced oscillation technique test effects an LTA(4)H dosed during challenge phase on AHR. Lung tissue lavage were collected for analysis.Treatment with improved multiple parameters encompassing AHR function. Significant decreases inflammatory leukocytes, cytokines, mucin observed lumen. Serum levels antigen-specific IgE IgG1 also decreased. Labeled antigen uptake dendritic cells subsequent trafficking draining lymph nodes decreased treatment. Provocatively, inhibition increased lipoxin fluid.These data suggest key driving Mechanistically, provide evidence LTA(4)H, affects recruitment both CD4(+) CD8(+) T cells, well nodes, may beneficially modulate other pro- antiinflammatory eicosanoids lung. Inhibition thus potential therapeutic strategy could aspects asthma.