Transepithelial neutrophil migration is CXCR1 dependent in vitro and is defective in IL-8 receptor knockout mice
Transepithelial neutrophil migration is CXCR1 dependent in vitro and is defective in IL-8 receptor knockout mice
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DOI：
10.4049/jimmunol.165.9.5287
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发表时间：
2000-11-01
影响因子：
4.4
通讯作者：
Svanborg, C
中科院分区：
文献类型：
--
作者：
Godaly, G;Hang, L;Svanborg, C
中性粒细胞在感染粘膜表面的迁移是趋化因子依赖性的，但趋化因子受体的作用尚未研究。在这项研究中，趋化因子受体被证明是表达上皮细胞内衬尿路，并发挥重要作用的中性粒细胞迁移通过粘膜屏障。尿路上皮CXCR 1和CXCR 2的表达在人类尿路活检中被检测到，并且在体外感染人类尿路上皮细胞系引起这两种受体的急剧增加。因此，IL-8与细胞的结合更高，并且IL-8依赖性中性粒细胞穿过感染的上皮细胞层的迁移增强。针对IL-8或CXCR 1受体的抗体抑制了这种增加60%（p < 0.004），但抗CXCR 2抗体没有作用，表明CXCR 1是该过程中更重要的受体。在小鼠泌尿道中进行了类似的观察，其中实验性感染刺激了鼠IL-8受体的上皮表达，随后中性粒细胞快速流入管腔。相反，IL-8受体敲除小鼠不能表达受体，它们的中性粒细胞不能穿过上皮屏障，并在组织中大量积累。这些结果表明，上皮细胞表达CXC受体，感染增加受体表达。此外，我们表明，CXCR 1是所需的中性粒细胞迁移在体外感染的上皮细胞层，和鼠IL-8受体是所需的中性粒细胞在体内穿过尿路感染的粘膜。
Neutrophil migration across infected mucosal surfaces is chemokine dependent, but the role of chemokine receptors has not been investigated. In this study, chemokine receptors were shown to be expressed by epithelial cells lining the urinary tract, and to play an essential role for neutrophil migration across the mucosal barrier. Uroepithelial CXCR1 and CXCR2 expression was detected in human urinary tract biopsies, and in vitro infection of human uroepithelial cell lines caused a dramatic increase in both receptors. As a consequence, there was higher binding of IL-8 to the cells and the IL-8-dependent neutrophil migration across the infected epithelial cell layers was enhanced. Abs to IL-8 or to the CXCR1 receptor inhibited this increase by 60% (p < 0.004), but anti-CXCR2 Abs had no effect, suggesting that CXCR1 was the more essential receptor in this process. Similar observations were made in the mouse urinary tract, where experimental infection stimulated epithelial expression of the murine IL-8 receptor, followed by a rapid flux of neutrophils into the lumen. IL-8 receptor knockout mice, in contrast, failed to express the receptor, their neutrophils were unable to cross the epithelial barrier, and accumulated in massive numbers in the tissues. These results demonstrate that epithelial cells express CXC receptors and that infection increases receptor expression. Furthermore, we show that CXCR1 is required for neutrophil migration across infected epithelial cell layers in vitro, and that the murine IL-8 receptor is needed for neutrophils to cross the infected mucosa of the urinary tract in vivo.