Site-specific dynamics of CD11b+ and CD103+ dendritic cell accumulations following ozone exposure

Brand JD, Ballinger CA, Tuggle KL, Fanucchi MV, Schwiebert LM, Postlethwait EM. Site-specific dynamics of CD11b(+) and CD103(+) dendritic cell accumulations following ozone exposure. Am J Physiol Lung Cell Mol Physiol 303: L1079-L1086, 2012. First published October 19, 2012; doi: 10.1152/ajplung.00185.2012.-Pulmonary dendritic cells (DCs) are among the first responders to inhaled environmental stimuli such as ozone (O-3), which has been shown to activate these cells. O-3 reacts with epithelial lining fluid (ELF) components in an anatomically site-specific manner dictated by O-3 concentration, airway flow patterns, and ELF substrate concentration. Accordingly, the anatomical distribution of ELF reaction products and airway injury are hypothesized to produce selective DC maturation differentially within the airways. To investigate how O-3 affects regional airway DC populations, we utilized a model of O-3-induced pulmonary inflammation, wherein C57BL/6 mice were exposed to 0.8 ppm O-3 8 h/day for 1, 3, and 5 days. This model induced mild inflammation and no remarkable epithelial injury. Tracheal, but not more distant airway sites, and mediastinal lymph node (MLN) DC numbers were increased significantly after the third exposure day. The largest increase in each tissue was of the CD103(+) DC phenotype. After 3 days of exposure, fewer DCs expressed CD80, CD40, and CCR7, and, at this same time point, total MLN T cell numbers increased. Together, these data demonstrate that O-3 exposure induced site-specific and phenotype changes in the pulmonary and regional lymph node DC populations. Possibly contributing to ozone-mediated asthma perturbation, the phenotypic changes to DCs within pulmonary regions may alter responses to antigenic stimuli. Decreased costimulatory molecule expression within the MLN suggests induction of tolerance mechanisms; increased tracheal DC number may raise the potential for allergic sensitization and asthmatic exacerbation, thus overcoming O-3-induced decrements in costimulatory molecule expression.