Cystic fibrosis epithelial cells have a receptor for pathogenic bacteria on their apical surface.
Cystic fibrosis epithelial cells have a receptor for pathogenic bacteria on their apical surface.
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DOI：
10.1073/pnas.92.7.3019
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发表时间：
1995-03
影响因子：
11.1
通讯作者：
L. Imundo;J. Barasch;A. Prince;Q. Al-Awqati
中科院分区：
文献类型：
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作者：
L. Imundo;J. Barasch;A. Prince;Q. Al-Awqati
铜绿假单胞菌在肺部的慢性定植和感染是囊性纤维化（CF）患者发病和死亡的主要原因。我们发现极化CF支气管和胰腺上皮细胞以可逆和剂量依赖性的方式结合铜绿假单胞菌。有显着更大的结合CF支气管和胰腺细胞比他们的配对拯救野生型CF跨膜传导调节。结合的铜绿假单胞菌很容易被未标记的铜绿假单胞菌取代，但不会被大肠杆菌取代，大肠杆菌是一种不会导致CF严重肺部疾病的微生物。相比之下，金黄色葡萄球菌（CF中常见的病原体）可以有效地将结合的铜绿假单胞菌从其受体中取代。我们发现唾液酸化不足的顶端蛋白质和更高浓度的无唾液酸神经节苷脂1（aGM 1）的顶端膜的CF相比，拯救上皮细胞。铜绿假单胞菌与aGM 1的孵育降低了其结合，用这种神经节苷脂的四糖部分（Gal β 1-3GalNAc β 1-4Gal β 1 -4Glc）处理上皮细胞也是如此。最后，抗aGM 1的抗体有效地将铜绿假单胞菌从其结合位点置换并阻断S.金黄色葡萄球菌对CF细胞而不是对拯救的细胞。这些结果表明aGM 1的四糖是铜绿假单胞菌和S.金黄色葡萄球菌，并且其在CF上皮细胞的顶膜中的增加的丰度使其成为CF肺中细菌感染的发病机制的可能贡献者。
Chronic colonization and infection of the lung with Pseudomonas aeruginosa is the major cause of morbidity and mortality in cystic fibrosis (CF) patients. We found that polarized CF bronchial and pancreatic epithelia bound P. aeruginosa in a reversible and dose-dependent manner. There was significantly greater binding to CF bronchial and pancreatic cells than to their matched pairs rescued with the wild-type CF transmembrane conductance regulator. Bound P. aeruginosa were easily displaced by unlabeled P. aeruginosa but not by Escherichia coli, an organism that does not cause significant pulmonary disease in CF. In contrast, Staphylococcus aureus, a frequent pathogen in CF, could effectively displace bound P. aeruginosa from its receptor. We found undersialylation of apical proteins and a higher concentration of asialoganglioside 1 (aGM1) in apical membranes of CF compared with rescued epithelia. Incubation of P. aeruginosa with aGM1 reduced its binding, as did treatment of the epithelia with the tetrasaccharide moiety of this ganglioside (Gal beta 1-3GalNAc beta 1-4Gal beta 1-4Glc). Finally, an antibody to aGM1 effectively displaced P. aeruginosa from its binding site and blocked binding of S. aureus to CF cells but not to rescued cells. These results show that the tetrasaccharide of aGM1 is a receptor for P. aeruginosa and S. aureus and that its increased abundance in the apical membrane of CF epithelia makes it a likely contributor to the pathogenesis of bacterial infections in the CF lung.