Receptor for advanced glycation end products (RAGE) is involved in cigarette smoke induced inflammation and emphysema

COPD is mostly caused by cigarette smoking and is characterized by alveolar tissue destruction and pulmonary inflammation. Previous studies have shown an increased expression of RAGE in patients with COPD. We investigated the role of RAGE in cigarette smoke (CS) induced inflammation and emphysema in mouse models of COPD. RAGE null mutant (RAGE-/-) and wild-type (WT) mice were exposed to CS for four days (acute) or six months (chronic). To investigate lung inflammation, bronchoalveolar lavage fluid (BALF) differential cell counts, and cytokine levels were analyzed. For the chronic model, pulmonary function was assessed by invasive measurements and the lung structure was determined by stereology. In the acute model, RAGE-/- mice showed a significant larger increase in cell numbers, mainly attributable to an influx of macrophages. In WT mice, the total cell number was lower and neutrophils represented the predominant cell type, also they had higher KC levels in the BALFs. Mice exposed to CS for six months showed no changes in any inflammatory marker. Pulmonary function and stereology showed that already without CS exposure, RAGE-/-mice had an increase in lung compliance and mean chord length, whereas the elastin expression was decreased. Chronic CS exposure did not cause additional changes in RAGE-/- mice. This study shows an involvement of RAGE in the pulmonary response to CS exposure. At early time points RAGE is involved in the regulation of acute inflammatory responses, while in the chronic exposure model RAGE-/- mice showed an altered pulmonary structure. RAGE is involved in pulmonary biology under normal conditions and determines the response to CS.