Crane I J, Wallace C A, McKillop-Smith S, Forrester J V
Department of Ophthalmology, University of Aberdeen Medical School, Foresterhill, Aberdeen, UK.
Immunology. 2000 Nov;101(3):426-33. doi: 10.1046/j.0019-2805.2000.01105.x.
Chemokine production at the blood-retina barrier probably plays a critical role in determining the influx of tissue-damaging cells from the circulation into the retina during inflammation. The blood-retina barrier comprises the retinal microvascular endothelium and the retinal pigment epithelium. Chemokine expression and production by human retinal microvascular endothelial cells (REC) have never been reported previously, so we examined the in vitro expression and production of monocyte chemoattractant protein-1 (MCP-1), regulated on activation of normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, interleukin (IL)-8, epithelial cell-derived neutrophil activating protein-78 (ENA-78) and growth related oncogene alpha (GROalpha) in these cells, both unstimulated and stimulated by cytokines likely to be present during the evolution of an inflammatory response. We compared this to expression and production of these chemokines in vitro in human retinal pigment epithelial cells (RPE). MCP-1 was expressed and produced constitutively by REC but all the chemokines were produced in greater amounts upon stimulation with the proinflammatory cytokines IL-1beta and tumour necrosis factor-alpha (TNF-alpha). MCP-1 and IL-8 were produced at much higher levels than the other chemokines tested. MIP-1alpha and MIP-1beta were present only at low levels, even after stimulation with IL-1beta and TNF-alpha. Cytokines with greater anti-inflammatory activity, such as IL-4, IL-10, IL-13, transforming growth factor-beta (TGF-beta) and IL-6, had little effect on chemokine production either by REC alone or after stimulation with IL-1beta and TNF-alpha. RPE, although a very different cell type, showed a similar pattern of expression and production of chemokines, indicating the site-specific nature of chemokine production. Chemokine production by REC and RPE is probably significant in selective leucocyte recruitment during the development of inflammation in the retina.
在炎症过程中，血视网膜屏障处趋化因子的产生可能在决定循环中组织损伤细胞流入视网膜的过程中起关键作用。血视网膜屏障由视网膜微血管内皮细胞和视网膜色素上皮细胞组成。此前从未报道过人类视网膜微血管内皮细胞（REC）趋化因子的表达和产生情况，因此我们检测了这些细胞在未受刺激以及受到炎症反应过程中可能存在的细胞因子刺激时，单核细胞趋化蛋白-1（MCP-1）、正常T细胞激活后表达和分泌的调节因子（RANTES）、巨噬细胞炎性蛋白（MIP）-1α、MIP-1β、白细胞介素（IL）-8、上皮细胞衍生的中性粒细胞激活蛋白-78（ENA-78）和生长相关癌基因α（GROα）的体外表达和产生情况。我们将此与人类视网膜色素上皮细胞（RPE）中这些趋化因子的体外表达和产生情况进行了比较。REC组成性表达并产生MCP-1，但在用促炎细胞因子IL-1β和肿瘤坏死因子-α（TNF-α）刺激后，所有趋化因子的产生量都增加。MCP-1和IL-8的产生水平远高于其他检测的趋化因子。即使在用IL-1β和TNF-α刺激后，MIP-1α和MIP-1β也仅以低水平存在。具有更强抗炎活性的细胞因子，如IL-4、IL-10、IL-13、转化生长因子-β（TGF-β）和IL-6，单独作用于REC或在用IL-1β和TNF-α刺激后，对趋化因子的产生几乎没有影响。RPE虽然是一种非常不同的细胞类型，但显示出类似的趋化因子表达和产生模式，表明趋化因子产生具有位点特异性。在视网膜炎症发展过程中，REC和RPE产生趋化因子可能在选择性白细胞募集中起重要作用。
