Abstract
Osteopontin (OPN) plays a role in inflammation via recruitment of neutrophils and tissue remodeling. In this study, we investigated the distribution of OPN-expressing cells in the airway epithelium of normal lung tissue and that from patients with chronic obstructive pulmonary disease (COPD). OPN was detected on the epithelial cell surface of small airways and in scattered cells within the epithelial cell layer. Staining revealed higher OPN concentrations in tissue showing moderate to severe COPD compared to that in controls. In addition, OPN expression was confined to goblet and club cells, and was absent from ciliated and basal cells as detected via immunohistochemistry. However, OPN expression was up-regulated in submerged basal cells cultures exposed to cigarette smoke (CS) extract. Cell fractioning of air-liquid interface cultures revealed increased OPN production from basal compartment cells compared to that in luminal fraction cells. Furthermore, both constitutive and CS-induced expression of OPN decreased during differentiation. In contrast, cultures stimulated with interleukin (IL)-13 to promote goblet cell hyperplasia showed increased OPN production in response to CS exposure. These results indicate that the cellular composition of the airway epithelium plays an important role in OPN expression and that these levels may reflect disease endotypes in COPD.
Highlights
chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow limitation due to chronic airway inflammation
COPD severity was staged according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification using the forced expiratory volume in 1 s (FEV1) after bronchodilation as previously described[27]
We investigated OPN distribution in epithelial cells of the small airways and showed that staining intensity was the highest in tissue from patients with COPD, those classified as GOLD stage II-III
Summary
COPD is characterized by irreversible airflow limitation due to chronic airway inflammation. Cigarette smoking is a major risk factor for the development and progression of COPD in industrialized societies[15] This heterogeneous disease comprises several phenotypes including the sub-type chronic bronchitis, which is characterized by increased mucus discharge and re-modeling of the airway epithelial lining (i.e., goblet cell hyperplasia)[16]. OPN contributed to airway matrix remodeling, an important event in COPD progression[19,20,21]. Another feature of COPD is prolonged and dysregulated inflammation, in which the epithelium plays key roles in neutrophil recruitment and macrophage activation, leading to excessive protease activity and the development of emphysema[16,22]. Our results indicate that OPN levels may reflect disease endotypes in chronic airway inflammation
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