Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 115, Issue 2, Pages 345-350Publisher
MOSBY, INC
DOI: 10.1016/j.jaci.2004.11.040
Keywords
inhaled LPS; phagocytosis; dendritic cell maturation
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Funding
- NCCIH NIH HHS [P01 AT002620] Funding Source: Medline
- NCRR NIH HHS [RR00046] Funding Source: Medline
- NHLBI NIH HHS [R01 HL62624, R01 HL66559, R01 HL062624, R01 HL062624-07] Funding Source: Medline
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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 How 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 pWmL; 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 GMCSF 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.
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