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.
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.
Authors: Jessica Wiser; Neil E Alexis; Qing Jiang; Weidong Wu; Carole Robinette; Robert Roubey; David B Peden Journal: Free Radic Biol Med Date: 2008-03-12 Impact factor: 7.376
Authors: William D Bennett; Neil E Alexis; Martha Almond; Margaret Herbst; Kirby L Zeman; David B Peden Journal: J Aerosol Med Pulm Drug Deliv Date: 2014-12 Impact factor: 2.849
Authors: Neil E Alexis; John C Lay; Milan Hazucha; Bradford Harris; Michelle L Hernandez; Philip A Bromberg; Howard Kehrl; David Diaz-Sanchez; Chong Kim; Robert B Devlin; David B Peden Journal: Inhal Toxicol Date: 2010-06 Impact factor: 2.724
Authors: Madeline A Dillon; Bradford Harris; Michelle L Hernandez; Baiming Zou; William Reed; Philip A Bromberg; Robert B Devlin; David Diaz-Sanchez; Steven Kleeberger; Haibo Zhou; John C Lay; Neil E Alexis; David B Peden Journal: Occup Environ Med Date: 2011-03-25 Impact factor: 4.402
Authors: Daniel G Olmedo; Deborah R Tasat; María Beatriz Guglielmotti; Rómulo Luis Cabrini Journal: J Mater Sci Mater Med Date: 2008-04-04 Impact factor: 3.896
Authors: Frank Schaumann; Meike Müller; Armin Braun; Birgit Luettig; David B Peden; Jens M Hohlfeld; Norbert Krug Journal: Am J Respir Crit Care Med Date: 2008-04-03 Impact factor: 21.405
Authors: Eva Lorenz; Marianne S Muhlebach; Philippe A Tessier; Neil E Alexis; R Duncan Hite; Michael C Seeds; David B Peden; Wayne Meredith Journal: Respir Med Date: 2007-12-27 Impact factor: 3.415