In vivo function of galectin-3 in motile cilia of airway epithelium

Abstract

Galectins, a family of beta-galactoside binding lectins, participate in an exceptionally broad range of biological processes. It has been established that galectin-3 localizes at the primary cilium in epithelial cells, and that the absence of galectin-3 leads to major growth defects in primary cilia. We have now extended these original observations by studying the consequences of galectin-3 null mutation on the biogenesis and function of motile cilia in vivo. Using confocal and electron microscopy, we show that endogenous galectin-3 is also located in the motile cilia of adult mouse tracheas. Ultrastructural studies reveal that the absence of galectin-3 leads to a large panel of cilium abnormalities, including swollen cilia, compound cilia, and also abnormal axonemal organization (deviations from the expected 9+2 microtubular organization). We also monitored ciliary beat patterns by high speed videomicroscopy. These experiments revealed that, although beating frequency is unchanged, the amplitude of the movement was drastically reduced in gal3-/tracheas. By following the dynamics of fluorescent beads applied to tracheal explants, we could demonstrate that the coordinated movement of the beads was severely affected in gal3-/tracheas, in comparison to wt tracheas. Collectively, these data establish that galectin-3 is required for correct biogenesis and function of motile cilia in adult mice. Despite these defects, gal3 mutant mice seem healthy in SPF animal house conditions. However, histological analyses and scanning electron microscopy revealed aberrant accumulation of mucus layers inside gal3-/tracheas, suggesting the mice suffer from insufficient mucociliary clearance.