Format

Send to

Choose Destination
J Allergy Clin Immunol. 2005 Feb;115(2):345-50.

Acute LPS inhalation in healthy volunteers induces dendritic cell maturation in vivo.

Author information

1
Center for Environmental Biology, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, NC 27599, USA. Neil_Axis@med.unc.edu

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.

CONCLUSION:

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.

PMID:
15696093
DOI:
10.1016/j.jaci.2004.11.040
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center