Opposite Roles of CCR2 and CX3CR1 Macrophages in Alkali-induced Corneal Neovascularization
Opposite Roles of CCR2 and CX3CR1 Macrophages in Alkali-induced Corneal Neovascularization
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DOI：
10.1097/ico.0b013e3181930bcd
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发表时间：
2009-06-01
期刊：
影响因子：
2.8
通讯作者：
Zhang, Xueguang
中科院分区：
文献类型：
--
作者：
Lu, Peirong;Li, Longbiao;Zhang, Xueguang
目的：探讨浸润性巨噬细胞在实验性角膜新生血管形成中的作用。方法：在巨噬细胞趋化因子受体CCR2或CX3CR1缺乏的小鼠，或在氯钠脂质体（Cl2MDP- lip）处理的小鼠中，碱损伤诱导角膜新生血管，氯钠脂质体可以选择性地消耗单核/巨噬细胞。用抗cd31抗体免疫染色法观察碱损伤后2周角膜新生血管的形成情况。采用反转录聚合酶链反应检测角膜内促血管生成因子和抗血管生成因子的表达。结果：ccr2缺失小鼠碱诱导的角膜新生血管形成减少，巨噬细胞浸润减少，而cx3cr1缺失小鼠碱诱导的角膜新生血管形成更严重，巨噬细胞浸润减少。抗cd31抗体免疫组化分析表明，C12MDP-lip处理的选择性巨噬细胞消耗对碱诱导的角膜新生血管没有影响，而角膜内巨噬细胞浸润明显减少。碱损伤增强了原血管生成分子的表达，包括基质金属蛋白酶-2、基质金属蛋白酶-9和肿瘤坏死因子α，以及抗血管生成因子的表达，包括溶栓素和具有血小板反应蛋白(ADAMTS)-1、血小板反应蛋白-1和血小板反应蛋白-2的金属蛋白酶。c12mdp唇处理小鼠显示这些分子的信使RNA表达减少。结论：由于表达CCR2-和cx3cr1的巨噬细胞在血管生成中表现出相反的活性，因此整体上巨噬细胞的消耗可能对碱诱导的角膜新生血管没有明显的影响。
Purpose: The purpose of this study was to investigate the role of infiltrating macrophages in the development of experimental corneal neovascularization.Methods: Corneal neovascularization was induced by alkali injury in mice deficient in a macrophage-tropic chemokine receptor, CCR2 or CX3CR1, or in mice treated with clodronate-liposomes (Cl2MDP- lip), which can selectively deplete monocytes/macrophages. Corneal neovascularization 2 weeks after alkali injury was assessed by immunostaining with anti-CD31 antibody. Intracorneal expression of proangiogenic and antiangiogenic factors was determined by rev transcription-polymerase chain reaction.Results: CCR2-deficient mice exhibited reduced alkali-induce corneal neovascularization with reduced macrophage infiltration, whereas CX3CR1-deficient mice developed a more severe form of alkali-induced corneal neovascularization with reduced macrophage infiltration. Selective macrophage depletion by C12MDP-lip treatment failed to affect alkali-induced corneal neovascularization as evidenced by immunohistochemical analysis using anti-CD31 antibody, whereas intracorneal macrophage infiltration was markedly reduced. Alkali injury enhanced the expression of proangiogemc molecules, including matrix metalloproteinase-2, matrix metalloproteinase-9, and tumor necrosis factor alpha, and antiangiogenic factors, including a disintegrin and metal loprotease with thrombospondin (ADAMTS)-1, thrombospondin-1, and thrombospondin-2. C12MDP-lip-treated mice exhibited a reduction in the messenger RNA expression of these molecules.Conclusion: Because CCR2- and CX3CR1-expressing macrophages exhibit opposite activities in angiogenesis, depletion of macrophages as a whole may not have apparent effects on alkali-induced corneal neovascularization.