Glycoconjugate Journal ( IF 3 ) Pub Date : 2020-07-14 , DOI: 10.1007/s10719-020-09935-x Nicoletta Loberto 1 , Giulia Mancini 1 , Rosaria Bassi 1 , Emma Veronica Carsana 1 , Anna Tamanini 2 , Nicoletta Pedemonte 3 , Maria Cristina Dechecchi 4 , Sandro Sonnino 1 , Massimo Aureli 1
Human primary bronchial epithelial cells differentiated in vitro represent a valuable tool to study lung diseases such as cystic fibrosis (CF), an inherited disorder caused by mutations in the gene coding for the Cystic Fibrosis Transmembrane Conductance Regulator. In CF, sphingolipids, a ubiquitous class of bioactive lipids mainly associated with the outer layer of the plasma membrane, seem to play a crucial role in the establishment of the severe lung complications. Nevertheless, no information on the involvement of sphingolipids and their metabolism in the differentiation of primary bronchial epithelial cells are available so far. Here we show that ceramide and globotriaosylceramide increased during cell differentiation, whereas glucosylceramide and gangliosides content decreased. In addition, we found that apical plasma membrane of differentiated bronchial cells is characterized by a higher content of sphingolipids in comparison to the other cell membranes and that activity of sphingolipids catabolic enzymes associated with this membrane results altered with respect to the total cell activities. In particular, the apical membrane of CF cells was characterized by high levels of ceramide and glucosylceramide, known to have proinflammatory activity. On this basis, our data further support the role of sphingolipids in the onset of CF lung pathology.
中文翻译:
分化过程中人原代支气管细胞中的鞘脂和质膜水解酶及其在囊性纤维化中的改变模式。
体外分化的人原代支气管上皮细胞代表了研究肺病的宝贵工具,例如囊性纤维化 (CF),这是一种由编码囊性纤维化跨膜电导调节器的基因突变引起的遗传性疾病。在 CF 中,鞘脂是一种普遍存在的生物活性脂质,主要与质膜的外层相关,似乎在严重肺部并发症的发生中起着至关重要的作用。然而,到目前为止,还没有关于鞘脂及其代谢参与初级支气管上皮细胞分化的信息。在这里,我们显示神经酰胺和球三糖神经酰胺在细胞分化过程中增加,而葡萄糖神经酰胺和神经节苷脂含量减少。此外,我们发现,与其他细胞膜相比,分化的支气管细胞的顶端质膜的特点是鞘脂含量更高,并且与该膜相关的鞘脂分解代谢酶的活性结果相对于总细胞活性发生了改变。特别是,CF 细胞的顶膜以高水平的神经酰胺和葡萄糖神经酰胺为特征,已知具有促炎活性。在此基础上,我们的数据进一步支持鞘脂在 CF 肺病理发病中的作用。CF 细胞的顶膜以高水平的神经酰胺和葡萄糖神经酰胺为特征,已知具有促炎活性。在此基础上,我们的数据进一步支持鞘脂在 CF 肺病理发病中的作用。CF 细胞的顶膜以高水平的神经酰胺和葡萄糖神经酰胺为特征,已知具有促炎活性。在此基础上,我们的数据进一步支持鞘脂在 CF 肺病理发病中的作用。