Increased galectin-3 expression and intra-epithelial neutrophils in small airways in severe COPD

Abstract

Galectins-1 and -3 regulate epithelial proliferation/apoptosis and neutrophil activation, and are implicated in lung cancer and asthma. The role of galectins in chronic obstructive pulmonary disease (COPD), characterised by epithelial changes and neutrophil infiltration, remains unknown.In the present study, galectin-1 and -3 expression was assessed by immunohistology in the bronchial epithelium of lung specimens from eight severe COPD patients and compared with nine nonsmokers and six smokers without COPD. Findings were related to epithelial proliferation (Ki-67), tissue inflammation and lung function.Epithelial galectin-3 immunostaining was increased only in the small airways of COPD patients when compared with nonsmokers and smokers. In contrast, galectin-1 was only significantly increased in the small airways of the group of smokers. Ki-67+ epithelial cells and neutrophils were increased in the small airways of COPD patients when compared with smokers. Furthermore, intra-epithelial neutrophils correlated in the small airways with Ki-67+ epithelial cells and with the forced expiratory volume in one second/forced vital capacity ratio. However, no correlation was observed with galectin expression.The present study supports the hypothesis that distal airways represent an important site for detecting changes in chronic obstructive pulmonary disease. In patients with severe disease, an increased galectin-3 expression and neutrophil accumulation in the small airway epithelium was demonstrated, correlating with epithelial proliferation and airway obstruction.

Effects of cigarette smoke extract on human airway smooth muscle cells in COPD

“…In our study we used ASM cells from smokers with and without COPD. The induction of CXCL8 and CXCL1 by CSE in ASM cells from both groups may reflect the observation that neutrophils are increased in COPD patients [31] and smokers without COPD [32]. Furthermore, as low concentrations of CSE induced CXCL1 in the COPD cells only, this suggested that these cells were hyperresponsive to CSE, and may explain why some smokers develop COPD and others do not.…”

Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction

“…Significant changes in oxidant responsive genes have been observed in the epithelium of healthy smokers as well as COPD patients [94]. A small increase in the proliferative rate of the epithelium of small airways of COPD patients has been reported [95], together with increased expression of galectin-1 in the epithelium, which could be involved in epithelial proliferation and apoptosis.…”

Cigarette smoke extract reduces VEGF in primary human airway epithelial cells

“…The results demonstrated that SAEC were more responsive to acute CSE exposure than NHBE cells, with regard to VEGF reduction. Although some reports have proposed certain differences of cellular population or gene expression, such as galectin-3 and Ki-67, in small and large AEC in COPD [43], no previous studies have addressed the molecular mechanisms responsible for the different responses to CS exposure between these two types of AEC. Further studies are needed to demonstrate the molecular basis upon which SAEC are more responsive to CSE exposure than NHBE cells with regard to VEGF reduction.…”