Peter Julius

Function-Associated Surface Molecules on Airway Dendritic Cells in Cigarette Smokers

Airway dendritic cells (DCs) control pulmonary immune responses to inhaled particles. However, the profile of function-associated surface molecules on airway DCs in smokers is unknown. In this study, function-associated surface molecules were analyzed using four-color flow cytometry on myeloid DCs (mDCs) in bronchoalveolar lavage fluid (BALF) of cigarette smokers and never-smokers. Furthermore, the lung function was assessed directly before bronchoscopy in all participants. There was a 7-fold increase in total cell numbers in BALF of smokers, as compared with never-smokers. The percentage of mDCs among BALF cells and the expression of the maturation marker CD83 on mDCs did not differ between smokers and never-smokers. However, there was a strong increase in the expression of Langerin and CD1a (markers of Langerhans cells) on mDCs of smokers. Furthermore, mDCs of smokers were characterized by an increased expression of antigen presentation markers such as CD80 and CD86. By contrast, mDCs of smokers displayed a decreased expression of the lymph node homing receptor CCR7, as compared with mDCs of never-smokers. Decreased expression of CCR7 on mDCs, but not any of the other surface molecules studied, was specifically associated with airway obstruction and pulmonary hyperinflation in smokers. In conclusion, our data suggest that smoking affects the expression profile of function-associated surface molecules on airway mDCs. We provide the first evidence that a reduced CCR7 expression on airway mDCs is associated with airflow limitation in smokers.

Anti-Inflammatory Actions of Histamine H1 Receptor Antagonists Unrelated to H1 Receptor Blockade

Histamine H1 receptor antagonists (antihistamines) are widely used for treatment of allergic conditions such as rhinitis, urticaria and atopic dermatitis. A number of first- and second-generation compounds are available; all prevent the pro-inflammatory pharmacological actions of histamine related to allergy and inflammation through competitive antagonism at H1 receptors. In addition, both in vitro and animal studies suggest that second-generation antihistamines may also show anti-inflammatory effects unrelated to H1 receptor antagonism. These effects include inhibition of the functions of several effector and regulator cells of inflammation, such as degranulation of mast cells, oxygen radical release from eosinophils and neutrophils, lipid mediator generation from eosinophils, and eosinophil cell migration. Although their precise mode of action is incompletely understood, H1 antagonists may interfere with cellular transmembrane signalling processes, including Ca++ transmembrane flux and intracellular mobilisation, accumulation of intracellular adenosine 3′,5′-monophosphate (cyclic AMP), and the activities of both protein kinase C and NADPH oxidase. Whether or not H1 antagonists mediate these effects via binding to histamine receptor subtypes other than H1 remains, as yet, unclear. This review discusses the clinical effects and the putative mode of anti-inflammatory action unrelated to H1 receptor blockade of this class of drugs.