Acute LPS inhalation in healthy volunteers induces dendritic cell maturation in vivo.
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.
Alexis
Neil E
NE
Center for Environmental Biology, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, NC 27599, USA. Neil_Axis@med.unc.edu
Lay
John C
JC
Almond
Martha
M
Bromberg
Philip A
PA
Patel
Dhavalkumar D
DD
Peden
David B
DB
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
D016207:Cytokines; D008070:Lipopolysaccharides