Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation.
Increased exposure to air pollutants such as diesel exhaust particles (DEP) has been proposed as one mechanism to explain the rise in allergic disorders. However, the immunologic mechanisms by which DEP enhance allergic sensitization and asthma remain unclear. We hypothesized that DEP act as an adjuvant for immature dendritic cell (DC) maturation via its effect on airway epithelial cell-derived microenvironment for DC. Immature monocyte-derived DC (iMDDC) failed to undergo phenotypic (CD80, CD83, CD86) or functional (T cell activation) maturation in response to exposure to DEP (0.001-100 mug/ml). In contrast, primary cultures of human bronchial epithelial cells (HBEC) treated with DEP induced iMDDC phenotypic maturation (2.6 +/- 0.1-fold increase in CD83 expression, n = 4, p < 0.05) and functional maturation (2.6 +/- 0.2-fold increase in T cell activation, n = 4, p < 0.05). Functional maturation of iMDDC was induced by conditioned medium derived from DEP-treated HBEC, and was inhibited in cultures with DEP-treated HBEC and blocking Abs against GM-CSF, or GM-CSF-targeted small interfering RNA. These data suggest that DEP induce Ag-independent DC maturation via epithelial cell-DC interactions mediated by HBEC-derived GM-CSF. Although additional signals may be required for polarization of DC, these data suggest a novel mechanism by which environmental pollutants alter airway immune responses.
Bleck
Bertram
B
Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, NY 10016, USA.
Tse
Doris B
DB
Jaspers
Ilona
I
Curotto de Lafaille
Maria A
MA
Reibman
Joan
J
D001980:Bronchi / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010316:Particle Size; D020545:Respiratory Mucosa / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D012995:Solubility; D001335:Vehicle Emissions
D001335:Vehicle Emissions; D016178:Granulocyte-Macrophage Colony-Stimulating Factor