Research Article: Receptor for advanced glycation endproducts (RAGE) maintains pulmonary structure and regulates the response to cigarette smoke

Date Published: July 5, 2017

Publisher: Public Library of Science

Author(s): Lisa Wolf, Christian Herr, Julia Niederstraßer, Christoph Beisswenger, Robert Bals, Thomas H Thatcher.

http://doi.org/10.1371/journal.pone.0180092

Abstract

The receptor for advanced glycation endproducts (RAGE) is highly expressed in the lung but its physiological functions in this organ is still not completely understood. To determine the contribution of RAGE to physiological functions of the lung, we analyzed pulmonary mechanics and structure of wildtype and RAGE deficient (RAGE-/-) mice. RAGE deficiency spontaneously resulted in a loss of lung structure shown by an increased mean chord length, increased respiratory system compliance, decreased respiratory system elastance and increased concentrations of serum protein albumin in bronchoalveolar lavage fluids. Pulmonary expression of RAGE was mainly localized on alveolar epithelial cells and alveolar macrophages. Primary murine alveolar epithelial cells isolated from RAGE-/- mice revealed an altered differentiation and defective barrier formation under in vitro conditions. Stimulation of interferone-y (IFNy)-activated alveolar macrophages deficient for RAGE with Toll-like receptor (TLR) ligands resulted in significantly decreased release of proinflammatory cytokines and chemokines. Exposure to chronic cigarette smoke did not affect emphysema-like changes in lung parenchyma in RAGE-/- mice. Acute cigarette smoke exposure revealed a modified inflammatory response in RAGE-/- mice that was characterized by an influx of macrophages and a decreased keratinocyte-derived chemokine (KC) release. Our data suggest that RAGE regulates the differentiation of alveolar epithelial cells and impacts on the development and maintenance of pulmonary structure. In cigarette smoke-induced lung pathology, RAGE mediates inflammation that contributes to lung damage.

Partial Text

The receptor for advanced glycation endproducts (RAGE) is a cell surface receptor and belongs to the immunoglobulin superfamily [1]. Under physiological conditions, RAGE is highly expressed in the lung, while in other organs and tissues its expression rate is very low [2]. The pulmonary localization of RAGE is mainly attributed to alveolar epithelial cells [2, 3]. In these cells, RAGE is involved in the cell adhesion to extracellular matrix proteins and supports the characteristic cell-specific morphology by enhancing their spreading and flattening [2].

The main finding of the present study is that RAGE participates in the maintenance of pulmonary mechanics and structure. We show that RAGE regulates the differentiation of alveolar epithelial cells and is involved in regulation of the alveolar barrier function. In CS-induced lung pathology, RAGE-mediates inflammation and has a role in subsequent damage of the lung structure.

 

Source:

http://doi.org/10.1371/journal.pone.0180092

 

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