Expression of receptor activator of nuclear factor‐κB (RANK), RANK ligand, and osteoprotegerin in the normal and E. coli lipopolysaccharide‐treated horse lungs

Abstract

Receptor activator of nuclear factor‐κB ligand (RANKL), its receptor RANK and antagonist osteoprotegerin (OPG) are members of the TNF receptor superfamily. RANKL/RANK signaling mediates TNFα‐induced inflammation and RANKL acts as a chemoattractant for immune cells. OPG interacts with and blocks RANKL signal transduction. There are no or little data on the expression of RANKL, RANK, and OPG in normal or inflamed lungs. Therefore, we studied their expression in control and lipopolysaccharide (LPS) treated horse lungs. Immunohistochemistry showed RANKL expression in alveolar/septal macrophages, vascular endothelium, and alveolar septum but not in airway epithelium in control horses. The LPS treatment increased RANKL expression in airway epithelium and alveolar septum. While a weak staining for RANK was detected in airway epithelium and vascular endothelium of control horse lungs, the expression was increased in airway epithelium of LPS‐treated horses. OPG was expressed in airway epithelium and alveolar/septal macrophages and was increased in LPS‐treated lungs. Immunoelectron microscopy detected all three molecules in pulmonary intravascular and alveolar macrophages. Western blot confirmed expression of all three molecules in the lungs. These data show LPS‐induced changes in the expression of RANK, RANKL, and OPG to suggest their roles in endotoxin‐induced lung inflammation.Grant Funding Source: NSERC