Conditional Overexpression of Receptors for Advanced Glycation End-Products in the Adult Murine Lung Causes Airspace Enlargement and Induces Inflammation

Receptors for advanced glycation end-products (RAGE) are multiligand surface receptors detected abundantly in pulmonary tissue. Our previous work revealed increased RAGE expression in cells and lungs exposed to tobacco smoke and RAGE-mediated cytokine expression via proinflammatory mechanisms involving NF-κB. RAGE expression is elevated in various pathological states, including chronic obstructive pulmonary disease; however, precise contributions of RAGE to the progression of emphysema and pulmonary inflammation in the adult lung are unknown. In the current study, we generated a RAGE transgenic (RAGE TG) mouse and conditionally induced adult alveolar epithelium to overexpress RAGE. RAGE was induced after the period of alveologenesis, from weaning (20 d of age) until animals were killed at 50, 80, and 110 days (representing 30, 60, and 90 d of RAGE overexpression). Hematoxylin and eosin staining and mean chord length revealed incremental dilation of alveolar spaces as RAGE overexpression persisted. TUNEL s...