Abstract

The receptor for advanced glycation end-products (RAGE) is an immunoglobulin superfamily cell adhesion molecule predominantly expressed in the lung, but its pulmonary importance is incompletely understood. Since RAGE alters the respiratory mechanics, which is also challenged by endurance running activity, we studied the RAGE-dependent effect of higher running activity on selected lung parameters in a long-term animal model using wild-type (WT) and RAGE knockout (RAGE-KO) mice. Higher long-term running activity of mice was ensured by providing a running wheel for 8 months. Recording the running activity revealed that RAGE-KO mice are more active than WT mice. RAGE-KO caused an increased lung compliance which additionally increased after long-term running activity with minor limitation of the expiratory flow, whereas the respiratory mechanics of WT mice remained constant. Although RAGE-KO mice had a less dense alveolar-capillary barrier for immune cells, higher long-term running activity led only in WT mice to more leukocyte infiltrations in the lung tissue and aggregations of lymphoid cells in the airways. In this regard, WT mice of the activity group were also more sensitive to ventilation-mediated airway damages. In contrast to RAGE-KO mice of the activity group, lungs of WT mice did not show an increase in the cAMP response element-binding protein, a transcription factor regulating many pro-survival genes. Our findings suggest an important role of RAGE in the physical capability due to its effect on the lung compliance as well as RAGE as a mediator of airway damages caused by higher long-term running activity.