Davies J, Dewar A, Bush A, Pitt T, Gruenert D, Geddes D M, Alton E W
Dept of Paediatric Respiratory Medicine, Imperial College at the National Heart and Lung Institute, London, UK.
Eur Respir J. 1999 Mar;13(3):565-70. doi: 10.1183/09031936.99.13356599.
The high incidence of colonization of the cystic fibrosis (CF) airway with Pseudomonas aeruginosa has been attributed to several mechanisms including increased numbers of asialoglycolipid receptors, which may be further increased by exposure to the bacterial exoproduct, neuraminidase. This study examined whether the adherence of P. aeruginosa to fresh CF respiratory epithelial cells can be reduced in vitro by anti-asialoGM1 (anti-aGM1) antibody, neuraminidase inhibition, or the use of asialoGM1 tetrasaccharide as a competitive inhibitor. CF nasal epithelial cells were incubated with a nonmucoid strain of P. aeruginosa, in the presence or absence of a polyclonal anti-aGM1 antibody, the neuraminidase inhibitor 2,3-dehydro-2-deoxy-N-acetyl-neuraminic acid (DANA), or the tetrasaccharide moiety of aGM1. Adherence of bacteria to the apical surface of ciliated epithelial cells was quantified using scanning electron microscopy. Incubation of the cells with bacteria in the presence of either anti-aGM1 antibody or DANA significantly reduced bacterial adherence by 51(7)%, (p<0.01), and 34(9)%, (p<0.01), respectively. In contrast, no significant effect on P. aeruginosa binding was seen in the presence of aGM1 tetrasaccharide. The data are consistent with previous studies on cultured cells, and suggest that the in vivo effects of such interventions should be explored as potential mechanisms to reduce Pseudomonas aeruginosa colonization in cystic fibrosis.
囊性纤维化(CF)气道被铜绿假单胞菌定植的高发生率归因于多种机制,包括去唾液酸糖脂受体数量增加,而暴露于细菌外产物神经氨酸酶可能会进一步增加该受体数量。本研究检测了抗去唾液酸GM1(抗-aGM1)抗体、神经氨酸酶抑制或使用去唾液酸GM1四糖作为竞争性抑制剂是否能在体外降低铜绿假单胞菌对新鲜CF呼吸道上皮细胞的黏附。将CF鼻上皮细胞与铜绿假单胞菌的非黏液型菌株一起孵育,同时存在或不存在多克隆抗-aGM1抗体、神经氨酸酶抑制剂2,3-脱氢-2-脱氧-N-乙酰神经氨酸(DANA)或aGM1的四糖部分。使用扫描电子显微镜对细菌黏附到纤毛上皮细胞顶端表面的情况进行定量。在抗-aGMl抗体或DANA存在的情况下,细胞与细菌一起孵育可使细菌黏附分别显著降低51(7)%,(p<0.01)和及多克隆抗-aGM1抗体、神经氨酸酶抑制剂2,3-脱氢-2-脱氧-N-乙酰神经氨酸(DANA)或aGM1的四糖部分。使用扫描电子显微镜对细菌黏附到纤毛上皮细胞顶端表面的情况进行定量。在抗-aGMl抗体或DANA存在的情况下,细胞与细菌一起孵育可使细菌黏附分别显著降低黏附分别显著降低51(%),(p<0.01)和及多克隆抗-aGM1抗体、神经氨酸酶抑制剂2,3-脱氢-2-脱氧-N-乙酰神经氨酸(DANA)或aGM1的四糖部分。使用扫描电子显微镜对细菌黏附到纤毛上皮细胞顶端表面的情况进行定量。在抗-aGMl抗体或DANA存在的情况下,细胞与细菌一起孵育可使细菌黏附分别显著降低黏附分别显著降低51(%),(p<0.01)和及多克隆抗-aGM1抗体、神经氨酸酶抑制剂2,3-脱氢-2-脱氧-N-乙酰神经氨酸(DANA)或aGM1的四糖部分。使用扫描电子显微镜对细菌黏附到纤毛上皮细胞顶端表面的情况进行定量。在抗-aGMl抗体或DANA存在的情况下,细胞与细菌一起孵育可使细菌黏附分别显著降低黏附分别显著降低51(%),(p<0.01)和34(9)%,(p<0.01)。相比之下,在aGM1四糖存在的情况下,未观察到对铜绿假单胞菌结合有显著影响。这些数据与先前对培养细胞的研究一致,并表明应探索此类干预措施在体内的作用,作为减少囊性纤维化中铜绿假单胞菌定植的潜在机制。 34(9)%,(p<0.01)。相比之下,在aGM1四糖存在的情况下,未观察到对铜绿假单胞菌结合有显著影响。这些数据与先前对培养细胞的研究一致,并表明应探索此类干预措施在体内的作用,作为减少囊性纤维化中铜绿假单胞菌定植的潜在机制。