Pincikova Terezia, Merikallio Heta, Kotortsi Ioanna, Karimi Reza, Li Chuan-Xing, Lappi-Blanco Elisa, Lindén Sara K, Padra Médea, Wheelock Åsa M, Nyrén Sven, Sköld Carl Magnus, Kaarteenaho Riitta L
Respiratory Medicine Unit, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institute, 171 76 Stockholm, Sweden.
Stockholm CF-Center, Albatross, K56, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
Int J Mol Sci. 2024 Dec 20;25(24):13653. doi: 10.3390/ijms252413653.
Mucins 5AC (MUC5AC) and 5B (MUC5B) are the major mucins providing the organizing framework for the airway's mucus gel. We retrieved bronchial mucosal biopsies and bronchial wash (BW) samples through bronchoscopy from patients with chronic obstructive pulmonary disease ( = 38), healthy never-smokers ( = 40), and smokers with normal lung function ( = 40). The expression of MUC5AC and MUC5B was assessed immunohistochemically. The mucin concentrations in BW were determined using the slot-blot technique. The immunohistochemical expression of MUC5AC and MUC5B was localized to goblet cells and submucosal glands. Smokers had higher MUC5AC and lower MUC5B goblet cell expression and higher concentrations of soluble MUC5AC in BW than never-smokers. The MUC5B expression in goblet cells correlated positively with expiratory air flows, diffusing capacity, and the dyspnoea score. Chronic bronchitis, emphysema, and the progression of chronic airflow limitation during a median follow-up time of 8.4 years were associated with higher MUC5AC and lower MUC5B expression in goblet cells. Sustainers, slow progressors, and rapid progressors of airflow obstruction differed in their MUC5B expression at baseline. Emphysema and bronchial wall thickening on CT at a follow-up visit were associated with lower MUC5B expression at baseline. Our findings strengthen the hypothesis that MUC5AC and MUC5B are yet another contributing factor to smoking-associated lung disease progression.
黏蛋白5AC(MUC5AC)和5B(MUC5B)是为气道黏液凝胶提供组织框架的主要黏蛋白。我们通过支气管镜检查从慢性阻塞性肺疾病患者(n = 38)、健康非吸烟者(n = 40)和肺功能正常的吸烟者(n = 40)中获取支气管黏膜活检组织和支气管灌洗(BW)样本。采用免疫组织化学方法评估MUC5AC和MUC5B的表达。使用狭缝印迹技术测定BW中的黏蛋白浓度。MUC5AC和MUC5B的免疫组织化学表达定位于杯状细胞和黏膜下腺。吸烟者的杯状细胞中MUC5AC表达高于非吸烟者,MUC5B表达低于非吸烟者,且BW中可溶性MUC5AC浓度更高。杯状细胞中MUC5B的表达与呼气气流、弥散能力和呼吸困难评分呈正相关。在8.4年的中位随访期内,慢性支气管炎、肺气肿和慢性气流受限的进展与杯状细胞中较高的MUC5AC表达和较低的MUC5B表达相关。气流阻塞的持续进展者、缓慢进展者和快速进展者在基线时的MUC5B表达存在差异。随访时CT上的肺气肿和支气管壁增厚与基线时较低的MUC5B表达相关。我们的研究结果强化了这样一种假设,即MUC5AC和MUC5B是吸烟相关肺部疾病进展的又一促成因素。