RECEPTOR FOR ADVANCED GLYCATION ENDPRODUCTS (RAGE) EXHIBITS HIGHLY DIFFERENTIAL CELLULAR AND SUBCELLULAR-LOCALIZATION IN RAT AND HUMAN LUNG

The transmembrane receptor (RAGE) of advanced glycation endproducts (A GEs), is abundantly present in the lung. Although the interaction of A GEs and RAGE plays an important role in vasculopathies, particularly i n diabetes, the lung is not a classical target organ of diabetes. Thus , the role of RAGE in the lung is still obscure. This study sought to precisely localise RAGE in the lungs of rat and human by immunohistoch emistry, double immunofluorescence and immunoelectron microscopy using a polyclonal antiserum developed against human recombinant RAGE. Anti -RAGE immunoreactivity was prominent in alveolar epithelial type I pne umocytes, while it was absent from type II pneumocytes and capillary e ndothelium. Cell type specificity was demonstrated by colocalisation w ith well established cell markers. Quantitative immunoelectron microsc opy of cryo-substituted, Lowicryl-embedded rat and human specimens dem onstrated a unique labelling pattern of RAGE in that it selectively lo calised to the basal cell membrane of type I pneumocytes. Labelling pa ttern was independent of the mode of fixation. Equivalent labelling de nsities were calculated from a fibrotic rat lung 3 months after irradi ation. This highly selective localisation of RAGE to the basal face of type I pneumocytes and its absence from capillary endothelium might e xplain the resistance of the lung to typical diabetic complications.