title: Acute LPS inhalation in healthy volunteers induces dendritic cell maturation in vivo.
abstract: BACKGROUND
  We have been studying the innate immune response of airways cells of healthy human volunteers to inhaled LPS, a Toll-like receptor 4 (TLR4) ligand, and have shown that macrophage phagocytic capacity is blunted.
  
  
  OBJECTIVE
  Because a primary feature of dendritic cell (DC) maturation is a loss of phagocytic capacity, we sought to determine whether acute LPS inhalation in healthy volunteers promotes DC maturation in vivo.
  
  
  METHODS
  Phagocytosis (IgG-opsonized zymosan particles) and cell-surface phenotypes were analyzed by flow cytometry of induced sputum cells obtained before and 6 hours after Clinical Center Reference Endotoxin (CCRE; 20,000 EU) inhalation in 9 healthy volunteers.
  
  
  RESULTS
  Neutrophils were elevated in the airways after CCRE inhalation (67% +/- 6% vs 37% +/- 6%; P < .05). Phagocytosis (monocytes, macrophages) was blunted (73%, 46%; P < .05) and negatively correlated with PMN influx ( R = -0.73; P < .05) after CCRE inhalation. GM-CSF and IL-1beta, potent DC maturation agents, were elevated after versus before CCRE inhalation (217 pg/mL +/- 103 pg/mL vs 722 pg/mL +/- 202 pg/mL; 83 pg/mL +/- 24 pg/mL vs 148 pg/mL +/- 37 pg/mL, respectively; P < .05). Markers of DC maturation (CD80, CD86, HLA-DR) were upregulated on monocytes and macrophages ( P < .05), and discrete populations of mature DC were observed ( P < .05) after CCRE inhalation.
  
  
  CONCLUSIONS
  Inhaled LPS, directly through TLR4 stimulation of immature DC and/or indirectly through stimulation of GM-CSF and IL-1beta, induces pulmonary DC maturation in vivo . Inhaled LPS may enhance allergic airways responses to air pollution through its ability to induce DC maturation.
authors.affiliation: Center for Environmental Biology, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, NC 27599, USA. Neil_Axis@med.unc.edu
authors.forename: Neil E
authors.initials: NE
authors.lastname: Alexis
authors.forename: John C
authors.initials: JC
authors.lastname: Lay
authors.forename: Martha
authors.initials: M
authors.lastname: Almond
authors.forename: Philip A
authors.initials: PA
authors.lastname: Bromberg
authors.forename: Dhavalkumar D
authors.initials: DD
authors.lastname: Patel
authors.forename: David B
authors.initials: DB
authors.lastname: Peden
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D016922:Cellular Senescence / Q000187:drug effects; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D010641:Phenotype; D012016:Reference Values; D013183:Sputum / Q000737:chemistry / Q000166:cytology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides