Blunting airway eosinophilic inflammation results in a decreased airway neutrophil response to inhaled LPS in patients with atopic asthma: a role for CD14.
Recent data demonstrate that atopic inflammation might enhance airway responses to inhaled LPS in individuals with atopic asthma by increasing CD14 expression on airway macrophages. We sought to determine whether blunting airway eosinophilic inflammation decreases CD14 expression and the subsequent airway polymorphonuclear neutrophil (PMN) response to inhaled LPS in subjects with atopic asthma. Twelve such subjects underwent a 2-week, placebo-controlled trial of inhaled steroid (440 microg fluticasone propionate [FP] twice per day); this was followed 48 hours later by an inhaled LPS (5 microg) challenge. A comparison of LPS-induced inflammatory cells in sputum, CD14 expression, and methacholine responsiveness with FP or placebo was conducted. Flow cytometry was used to analyze membrane-bound CD14 expression (mean fluorescence intensity) on sputum macrophages. We report that 48 hours before inhaled LPS challenge (baseline), FP significantly blunted airway eosinophils (cells per milligram; P =.04) and mCD14 expression (mean fluorescence intensity; P =.03) but did not decrease the number of PMNs (cells per milligram). Six hours after LPS challenge, airway PMNs and mCD14 expression were significantly decreased for FP in comparison with placebo (P =.04). Our data suggest that decreasing airway allergic inflammation with corticosteroids results in both decreased expression of CD14 on airway monocytic cells and a decreased PMN response to inhaled LPS.
Alexis
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NE
Center for Environmental Medicine and Lung Biology, Department of Pediatrics and Medicine, University of North Carolina-Chapel Hill 27599-7310, USA.
Peden
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DB
D000328:Adult; D000730:Androstadienes / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000276:immunology*; D002452:Cell Count; D005260:Female; D000068298:Fluticasone; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011657:Pulmonary Eosinophilia / Q000188:drug therapy / Q000276:immunology*; D013183:Sputum / Q000166:cytology
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D000068298:Fluticasone