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Houda Tahiri, Samy Omri, Chun Yang, François Duhamel, Sylvain Chemtob, Pierre Hardy; The Involvement of CD36 in Antiangiogenic Effects of Lymphocyte-Derived Microparticles on Choroidal Neovscularization. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):186.
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© ARVO (1962-2015); The Authors (2016-present)
Pathological choroidal neovascularization (CNV) is the major cause of severe vision loss in patients with age-related macular degeneration (AMD). Macrophages play important roles in CNV. The scavenger receptor CD36 mediates antiangiogenic effect, which is highly expressed in retinal pigment epithelium, microvascular endothelial cells and macrophages. Previously, we have demonstrated that human T-lymphocyte-derived microparticles (LMPs) are capable of modulating macrophages activities. This study is aimed to determine whether CD36 is involved in LMPs-induced antiangiogenic effect in choroidal angiogenesis.
LMPs were produced from apoptotic human T lymphocytes after treated with actinomycin D. The effects of LMPs on macrophages were determined using apoptosis assay and migration assay. Gene expression in LMPs-treated macrophages was evaluated by quantitative RT-PCR and RNA array. The expression of specific genes such as IL-10, IL-12, CD206, MCP-1 was determined by FACS analysis. Cell growth and cell proliferation of human retinal microvascular endothelial cells was also assessed after co-cultured with LMPs pre-treated macrophages. The uptake experiment was performed to determine the involvement of CD36 receptor. In vivo, the antiangiogenic effect of LMPs was investigated in laser-induced CNV model, and the CNV was quantified on choroidal flat-mounts. Immunohistostaining was performed to reveal the angiogenesis-related factors expression by macrophages in CNV areas.
LMPs dose-dependently inhibited macrophages cell growth without inducing cell death. LMPs-pretreated macrophages exhibited strong inhibitory effect on endothelial cell growth and this effect was associated with decreased expression of proangiogenic factor VEGF and increased antiangiogenic factors PEDF. The LMPs uptake by macrophages is reduced by 60% after CD36 antibody treatment. In vivo, intravitreal injection of LMPs significantly suppressed laser-induced CNV this antiangiogenic effect was less effective in CD36 deficient (CD36<br /> KO) mice.
LMPs are potent antiangiogenic reagent. Our study revealed that LMPs by macrophages is partially but significantly dependent on CD36, and LMPs may interfere with the proangiogenic environment through modulation of macrophages function.
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