RAGE targeting leads to protection from hyperoxia‐induced lung injury

Abstract

Critically ill patients often require supplemental oxygen during treatment; however the impact of hyperoxia on pulmonary biology is not well established. Receptors for advanced glycation end‐products (RAGE) are multiligand Type I cell surface receptors that influence development and cigarette smoke‐induced inflammation (Reynolds et al, 2007), but studies that address the role of RAGE in acute lung injury are insufficient. RAGE null mice exposed to hyperoxia survived 3 days longer than age‐matched wild‐type mice (9 vs. 6 days). After four days in hyperoxia, RAGE null mice had lower total cell infiltration into the airway, including PMNs and macrophages, and decreased total protein leak. Additionally, an inflammatory cytokine antibody array (Chemicon) and Western blotting revealed decreased secretion of several pro‐inflammtory molecules in lavage fluid obtained from RAGE knock out mice when compared to wild‐type. These data reveal that RAGE targeting leads to a diminished hyperoxia‐induced pulmonary inflammatory response. Further research into the role of RAGE signaling in the lung should identify novel targets likely to be important in the therapeutic alleviation of lung injury and associated persistent inflammation. Supported by the Flight Attendants Medical Research Institute (FAMRI, PRR) and the Parker B. Francis Foundation (PRR).