Kirkham Sara, Kolsum Umme, Rousseau Karine, Singh Dave, Vestbo Jørgen, Thornton David J
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
Am J Respir Crit Care Med. 2008 Nov 15;178(10):1033-9. doi: 10.1164/rccm.200803-391OC. Epub 2008 Sep 5.
Overproduction of mucus is a contributory factor in the progression of chronic obstructive pulmonary disease (COPD). The polymeric mucins are major macromolecules in the secretion. Therefore, we hypothesized that the polymeric mucin composition or properties may be different in the sputum from individuals with COPD and smokers without airflow obstruction.
To determine the major polymeric mucins in COPD sputum and whether these are different in the sputum from individuals with COPD compared with that from smokers without airflow obstruction.
The polymeric mucin composition of sputum from patients with COPD and smokers without airflow obstruction was analyzed by Western blotting analysis. The tissue localization of the mucins was determined by immunohistochemistry, and their size distribution was analyzed by rate-zonal centrifugation.
MUC5AC and MUC5B were the major mucins. MUC5AC was the predominant mucin in the smoker group, whereas MUC5B was more abundant from the patients with COPD, with a significant difference in the ratio of MUC5B to MUC5AC (P = 0.004); this ratio was correlated with FEV(1) in the COPD group (r = 0.63; P = 0.01). The lower-charged glycosylated form of MUC5B was more predominant in COPD (P = 0.012). No significant associations were observed with respect to sex, age, or pack-year history. In both groups, MUC5AC was produced by surface epithelial cells and MUC5B by submucosal gland cells. Finally, there was a shift toward smaller mucins in the COPD group.
Our data indicate that there are differences in mucin amounts and properties between smokers with and without COPD. Further studies are needed to examine how this may impact disease progression.
黏液过度产生是慢性阻塞性肺疾病(COPD)进展的一个促成因素。聚合黏蛋白是分泌物中的主要大分子。因此,我们推测COPD患者与无气流受限的吸烟者痰液中的聚合黏蛋白组成或特性可能不同。
确定COPD痰液中的主要聚合黏蛋白,以及与无气流受限的吸烟者痰液相比,COPD患者痰液中的这些黏蛋白是否存在差异。
通过蛋白质免疫印迹分析对COPD患者和无气流受限的吸烟者痰液中的聚合黏蛋白组成进行分析。通过免疫组织化学确定黏蛋白的组织定位,并通过速率区带离心分析其大小分布。
MUC5AC和MUC5B是主要的黏蛋白。MUC5AC是吸烟组中的主要黏蛋白,而MUC5B在COPD患者中更为丰富,MUC5B与MUC5AC的比例有显著差异(P = 0.004);该比例与COPD组中的第1秒用力呼气容积(FEV₁)相关(r = 0.63;P = 0.01)。电荷较低的糖基化形式的MUC5B在COPD中更为主要(P = 0.012)。在性别、年龄或吸烟包年史方面未观察到显著关联。在两组中,MUC5AC由表面上皮细胞产生,MUC5B由黏膜下腺细胞产生。最后,COPD组中黏蛋白向较小尺寸发生了偏移。
我们的数据表明,有气流受限的吸烟者与无气流受限的吸烟者在黏蛋白数量和特性上存在差异。需要进一步研究来探讨这可能如何影响疾病进展。