title: CD14-dependent airway neutrophil response to inhaled LPS: role of atopy.
abstract: BACKGROUND
  Inhaled endotoxin (LPS) is associated with airway neutrophilic (PMN) inflammation in both asthmatic and control subjects, with asthmatic subjects demonstrating possibly higher sensitivity. CD14 is the principal receptor mediating LPS responses in vivo. It is unknown whether constitutive CD14 can predict the magnitude of the PMN response after LPS inhalation and whether atopy plays a role in this response.
  
  
  OBJECTIVE
  We sought to examine associations between constitutive airway CD14 expression and LPS-induced PMNs after 5 microg of LPS inhalation and to examine associations between markers of atopy (eosinophils and eosinophil cationic protein) and CD14 expression and LPS-induced PMNs.
  
  
  METHODS
  Ten atopic asthmatic subjects and 8 healthy control subjects inhaled 0.9% saline and LPS (Escherichia coli 026:B6, 5 microg) separated by 3 weeks. Induced sputum was collected at 24 hours before and 6 hours after inhalation. Induced sputum was analyzed for total and differential cell counts and soluble markers (soluble [s]CD14, eosinophil cationic protein, IL8, and total protein). Flow cytometry was used to analyze membrane-bound CD14 expression.
  
  
  RESULTS
  Significant associations were found between the LPS-induced PMN response (PMNs per milligram of sputum) and both constitutive sCD14 (R = 0.7, P =.005) and membrane-bound CD14 (R = 0.9, P =.01). Asthmatic subjects demonstrated significantly higher levels of constitutive sCD14 compared with control subjects, and baseline eosinophils were significantly associated with baseline sCD14 (R = 0.7, P =.01) and LPS-induced PMNs (R = 0.6, P =.03).
  
  
  CONCLUSIONS
  Constitutive airway CD14 expression can predict the magnitude of the PMN response after inhaled LPS. Atopy appears to play a role in the level of CD14 expression and may contribute to LPS sensitivity in asthmatic subjects.
authors.affiliation: Center For Environmental Medicine and Lung Biology, Department of Pediatrics, University of North Carolina-Chapel Hill, 27599-7310, USA.
authors.forename: N
authors.initials: N
authors.lastname: Alexis
authors.forename: M
authors.initials: M
authors.lastname: Eldridge
authors.forename: W
authors.initials: W
authors.lastname: Reed
authors.forename: P
authors.initials: P
authors.lastname: Bromberg
authors.forename: D B
authors.initials: DB
authors.lastname: Peden
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis; D047091:Eosinophil Granule Proteins; D015870:Gene Expression; D005838:Genotype; D006720:Homozygote; D006801:Humans; D006969:Hypersensitivity, Immediate; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012137:Respiratory System / Q000166:cytology*; D012260:Ribonucleases; D013183:Sputum / Q000166:cytology
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012260:Ribonucleases