You Jian-Jang, Yang Chang-Hao, Huang Jen-Shang, Chen Muh-Shy, Yang Chung-May
Department of Ophthalmology, Keelung General Hospital, Department of Health, The Executive Yuan, Keelung, Taiwan.
Invest Ophthalmol Vis Sci. 2007 Nov;48(11):5290-8. doi: 10.1167/iovs.07-0187.
Fractalkine (FKN) is a chemoattractant and adhesion molecule for leukocytes. Angiogenic effect of FKN also has been reported. This study was an investigation of FKN-mediated angiogenesis in vitro and in vivo to determine its role in ocular angiogenic disorders.
FKN effects on cultured human umbilical vein endothelial cells (HUVECs) and bovine retinal capillary endothelial cells (BRECs) were evaluated with chemotaxis assay and a synthetic matrix capillary tube formation assay in vitro. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were used to detect mRNA and protein expression of FKN and its receptor, CX3CR1, in HUVECs and BRECs. A rabbit corneal neovascularization assay and an oxygen-induced retinopathy (OIR) model of mice were used to test the angiogenic property of FKN in vivo. FKN levels of vitreous samples from patients with proliferative diabetic retinopathy were measured by enzyme-linked immunosorbent assay (ELISA). Immunodepletion of FKN in PDR vitreous samples by anti-FKN polyclonal antibody was observed in endothelial cell chemotaxis assays.
FKN significantly induced migration of HUVECs and BRECs. FKN induced formation of endothelial cell capillary tubes on synthetic matrix. Expression of FKN and CX3CR1 was detected in HUVECs and BRECs by RT-PCR and Western blot analysis. FKN significantly induced more blood vessel growth than did the control in the rabbit corneal pocket neovascularization assay. Intravitreal injection of anti-mouse FKN antibody decreased retinal angiogenesis in the OIR model. The vitreous level of FKN was elevated in patients with PDR compared with control subjects. Immunodepletion of soluble FKN from PDR vitreous samples caused 36.6% less migration of BRECs.
FKN is an angiogenic mediator in vitro and in vivo. The vitreous level of FKN was elevated in patients with PDR. FKN may play an important role in ocular angiogenic disorders such as PDR.
趋化因子（FKN）是一种白细胞趋化因子和黏附分子。FKN的血管生成作用也有报道。本研究旨在体外和体内研究FKN介导的血管生成，以确定其在眼部血管生成性疾病中的作用。
采用趋化试验和合成基质毛细管形成试验在体外评估FKN对培养的人脐静脉内皮细胞（HUVEC）和牛视网膜毛细血管内皮细胞（BREC）的作用。采用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹分析检测HUVEC和BREC中FKN及其受体CX3CR1的mRNA和蛋白表达。采用兔角膜新生血管试验和小鼠氧诱导视网膜病变（OIR）模型在体内检测FKN的血管生成特性。采用酶联免疫吸附测定（ELISA）检测增殖性糖尿病视网膜病变患者玻璃体内FKN水平。在内皮细胞趋化试验中观察抗FKN多克隆抗体对增殖性糖尿病视网膜病变玻璃体内样本中FKN的免疫清除作用。
FKN显著诱导HUVEC和BREC迁移。FKN诱导合成基质上内皮细胞毛细管形成。通过RT-PCR和蛋白质印迹分析在HUVEC和BREC中检测到FKN和CX3CR1的表达。在兔角膜袋新生血管试验中，FKN比对照组显著诱导更多血管生长。玻璃体内注射抗小鼠FKN抗体减少了OIR模型中的视网膜血管生成。与对照组相比，增殖性糖尿病视网膜病变患者玻璃体内FKN水平升高。增殖性糖尿病视网膜病变玻璃体内样本中可溶性FKN的免疫清除导致BREC迁移减少36.6%。
FKN在体外和体内均为血管生成介质。增殖性糖尿病视网膜病变患者玻璃体内FKN水平升高。FKN可能在增殖性糖尿病视网膜病变等眼部血管生成性疾病中起重要作用。
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