Hedlund M, Duan R D, Nilsson A, Svanborg C
Department of Laboratory Medicine, Lund University, Sweden.
Mol Microbiol. 1998 Sep;29(5):1297-306. doi: 10.1046/j.1365-2958.1998.01017.x.
Uropathogenic Escherichia coli attach to epithelial cells through P fimbriae that bind Galalpha1-4Galbeta-oligosaccharide sequences in cell surface glycosphingolipids. The binding of P-fimbriated E. coli to uroepithelial cells causes the release of ceramide, activation of the ceramide signalling pathway and a cytokine response in the epithelial cells. The present study examined the molecular source of ceramide in human kidney A498 cells exposed to P-fimbriated E. coli. Agonists such as TNF-alpha and IL-1beta released ceramide from sphingomyelin by the activation of endogenous sphingomyelinases and hydrolysis of sphingomyelin, and triggered an IL-6 response. P-fimbriated E. coli caused a slight increase in endogenous sphingomyelinase activity, but there was no associated sphingomyelin hydrolysis. Instead, the concentration of galactose-containing glycolipids decreased. We propose that P-fimbriated E. coli differ from other activators of the ceramide pathway, in that release of ceramide is from receptor glycolipids and not from sphingomyelin. Receptor breakdown may be an efficient host defence strategy, as it reduces the concentration of cell surface receptors, releases soluble receptor analogues and activates an inflammatory response.
致病性大肠杆菌通过P菌毛附着于上皮细胞，P菌毛可与细胞表面糖鞘脂中的Galα1-4Galβ-寡糖序列结合。带有P菌毛的大肠杆菌与尿道上皮细胞的结合会导致神经酰胺释放，激活神经酰胺信号通路，并在上皮细胞中引发细胞因子反应。本研究检测了暴露于带有P菌毛大肠杆菌的人肾A498细胞中神经酰胺的分子来源。诸如肿瘤坏死因子-α和白细胞介素-1β等激动剂通过激活内源性鞘磷脂酶和鞘磷脂水解从鞘磷脂中释放神经酰胺，并引发白细胞介素-6反应。带有P菌毛的大肠杆菌使内源性鞘磷脂酶活性略有增加，但未伴随鞘磷脂水解。相反，含半乳糖糖脂的浓度降低。我们提出，带有P菌毛的大肠杆菌与神经酰胺途径的其他激活剂不同，其神经酰胺的释放来自受体糖脂而非鞘磷脂。受体分解可能是一种有效的宿主防御策略，因为它降低了细胞表面受体的浓度，释放了可溶性受体类似物并激活了炎症反应。
