Acute LPS inhalation in healthy volunteers induces dendritic cell maturation in vivo - 18/08/11
, John C. Lay, DVM, PhD a, Martha Almond, RRT a, Philip A. Bromberg, MD a, d, Dhavalkumar D. Patel, MD, PhD a, c, David B. Peden, MD, MS a, b
Reprint requests: Neil E Alexis, PhD, 104 Mason Farm Rd, Chapel Hill, NC 27599-7310.Chapel Hill, NC
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-1β, 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-1β, induces pulmonary DC maturation in vivo. Inhaled LPS may enhance allergic airways responses to air pollution through its ability to induce DC maturation.
Le texte complet de cet article est disponible en PDF.Key words : Inhaled LPS, phagocytosis, dendritic cell maturation
Abbreviations used : CBC, CCRE, DC, iDC, mDC, MFI
Plan
| Supported by National Institutes of Health grants RO1 HL62624 and RO1 HL66559 from the National Heart, Lung, and Blood Institute, P01AT002620 from the National Center for Complementary and Alternative Medicine, RR00046 from the General Clinical Research Centers program of the National Institutes of Health Division of Research Resources, and cooperative agreement CR-829522 from the US Environmental Protection Agency. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Heart, Lung, and Blood Institute, the National Center for Complementary and Alternative Medicine, the National Institutes of Health, or the US Environmental Protection Agency. |
Vol 115 - N° 2
P. 345-350 - février 2005 Retour au numéro
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