Monocyte chemoattractant protein 1 and fractalkine play opposite roles in angiogenesis via recruitment of different macrophage subtypes
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Pei-Rong Lu. Department of Ophthalmology, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China. lupeirong@suda.edu.cn; Gao-Qin Liu. Department of Ophthalmology, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China. liugaoqin2006@sina.com

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Supported by the National Natural Science Foundation of China (No.30972712; No.31600736; No.81671641); Jiangsu Province’s Key Provincial Talents Program (No.RC2011104); the Natural Science Foundation of Jiangsu Province of China (No.BK20151208); Jiangsu Provincial Medical Youth Talent (No.QNRC2016718); the Soochow Scholar Project of Soochow University (No.R5122001); Jiangsu Provincial Medical Innovation Team (No.CXTDA2017039).

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    Abstract:

    AIM: To explore the interaction between macrophages and chemokines [monocyte chemoattractant protein 1 (MCP-1/CCL2) and fractalkine/CX3CL1] and the effects of their interaction on neovascularization. METHODS: Human peripheral blood mononuclear cells, donated by healthy volunteers, were separated and cultured in RPMI-1640 medium containing 10% fetal bovine serum, then induced into macrophages by stimulation with 30 μg/L granulocyte macrophage-colony stimulating factor (GM-CSF). The expression of CCR2 and/or CX3CR1 in the macrophages was examined using flow cytometry. Macrophages were then stimulated with recombinant human CCL2 (rh-CCL2) or recombinant human CX3CL1 (rh-CX3CL1). The expression of angiogenesis-related genes, including VEGF-A, THBS-1 and ADAMTS-1 were examined using real-time quantitative polymerase chain reaction (PCR). Supernatants from stimulated macrophages were used in an assay of human retinal endothelial cell (HREC) proliferation. Finally, stimulated macrophages were co-cultured with HREC in a migration assay. RESULTS: The expression rate of CCR2 in macrophages stimulated by GM-CSF was 42%±1.9%. The expression rate of CX3CR1 was 71%±3.3%. Compared with vehicle-treated groups, gene expression of VEGF-A in the macrophages was greater in 150 mg/L CCL2-treated groups (P<0.05), while expression of THBS-1 and ADAMTS-1 was significantly lower (P<0.05). By contrast, compared with vehicle-treated groups, expression of VEGF-A in 150 mg/L CX3CL1-treated groups was significantly lower (P<0.05), while expression of THBS-1 and ADAMTS-1 was greater (P<0.05). Supernatants from CCL2 treated macrophages promoted proliferation of HREC (P<0.05), while supernatants from CX3CL1-treated macrophages inhibited the proliferation of HREC (P<0.05). HREC migration increased when co-cultured with CCL2-treated macrophages, but decreased with CX3CL1-treated macrophages (P<0.05). CONCLUSION: CCL2 and CX3CL1 exert different effects in regulation of macrophage in expression of angiogenesis-related factors, including VEGF-A, THBS-1 and ADAMTS-1. Our findings suggest that CCL2 and CX3CL1 may be candidate proteins for further exploration of novel targets for treatment of ocular neovascularization.

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Lei Chen, Gao-Qin Liu, Hong-Ya Wu, et al. Monocyte chemoattractant protein 1 and fractalkine play opposite roles in angiogenesis via recruitment of different macrophage subtypes. Int J Ophthalmol, 2018,11(2):216-222

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Publication History
  • Received:May 24,2017
  • Revised:December 08,2017
  • Adopted:
  • Online: February 06,2018
  • Published: