CCL3 production by microglial cells modulates disease severity in murine models of retinal degeneration.
CCL3 production by microglial cells modulates disease severity in murine models of retinal degeneration.
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DOI：
10.4049/jimmunol.1301738
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发表时间：
2014-04-15
期刊：
影响因子：
--
通讯作者：
Maeda A
中科院分区：
文献类型：
--
作者：
Kohno H;Maeda T;Perusek L;Pearlman E;Maeda A
许多退行性视网膜疾病说明视网膜炎性变化，包括小胶质细胞和巨噬细胞浸润到视网膜下腔。在目前的研究中，我们研究了趋化因子在Stargardt病的Abca 4-/-Rdh 8-/-小鼠模型和视网膜色素变性的Mertk-/-小鼠模型中的作用。对84种趋化因子和相关分子的PCR阵列分析显示，在Abca 4-/-Rdh 8-/-小鼠中，光照24 h后Ccl 3（MIP-1a）的表达增加了84.6倍。只有MIP-1趋化因子，包括Ccl 3和Ccl 4，在光照后24 h显示峰值表达，并且比其他趋化因子更早达到峰值。仅在小胶质细胞中记录了Ccl 3的分泌，而小胶质细胞和RPE细胞都产生Ccl 2。将Cx 3Cr 1gfp/Δ Abca 4-/-Rdh 8-/-小鼠暴露于强光导致视网膜下腔中出现Cx 3Cr 1GFP+单核细胞。为了解决CCL 3在视网膜变性中的体内作用，产生Ccl 3-/-Abca 4-/-Rdh 8-/-小鼠和Ccl 3-/-Mertk-/-小鼠。在强光暴露后，与Abca 4-/-Rdh 8-/-小鼠相比，Ccl 3-/-Abca 4-/-Rdh 8-/-小鼠表现出持续的视网膜炎症，在视网膜下腔中出现Iba-1阳性细胞，严重的感光细胞死亡和增加的Ccl 4表达。相比之下，Ccl 3-/-Abca 4-/-Rdh 8-/-小鼠在室内光照条件下在年龄相关的慢性视网膜变性中表现出比Abca 4-/-Rdh 8-/-小鼠更温和的视网膜炎症和变性。Ccl 3的缺乏也减轻了Mertk-/-小鼠中视网膜变性的严重程度。总之，我们的结果表明，Ccl 3在调节这些小鼠模型中视网膜炎症和变性的严重程度方面具有重要作用。
Many degenerative retinal diseases illustrate retinal inflammatory changes that include infiltration of microglia and macrophages into the subretinal space. In the current study, we examined the role of chemokines in the Abca4-/-Rdh8-/- mouse model of Stargardt disease and the Mertk-/- mouse model of retinitis pigmentosa. PCR array analysis of 84 chemokines and related molecules revealed 84.6-fold elevated expression of Ccl3 (MIP-1a) 24 h after light exposure in Abca4-/-Rdh8-/- mice. Only MIP-1 chemokines, including Ccl3 and Ccl4, displayed peak expression 24 h after light exposure, and peaked earlier than the other chemokines. Secretion of Ccl3 was documented only in microglia whereas both microglia and RPE cells produced Ccl2. Exposure of Cx3Cr1gfp/ΔAbca4-/-Rdh8-/- mice to intense light resulted in the appearance of Cx3Cr1GFP+ monocytes in the subretinal space. To address the in vivo role of CCL3 in retinal degeneration, Ccl3-/-Abca4-/-Rdh8-/- mice and Ccl3-/-Mertk-/- mice were generated. Following intense light exposure, Ccl3-/-Abca4-/-Rdh8-/- mice displayed persistent retinal inflammation with appearance of Iba-1-positive cells in the subretinal space, severe photoreceptor cell death and increased Ccl4 expression compared with Abca4-/-Rdh8-/- mice. In contrast, Ccl3-/-Abca4-/-Rdh8-/- mice exhibited a milder retinal inflammation and degeneration than Abca4-/-Rdh8-/- mice in age-related chronic retinal degeneration under room light conditions. The deficiency of Ccl3 also attenuated the severity of retinal degeneration in Mertk-/- mice. Taken together, our results indicate that Ccl3 has an essential role in regulating the severity of retinal inflammation and degeneration in these mouse models.
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DOI：
10.1084/jem.20080421
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Getts DR;Terry RL;Getts MT;Müller M;Rana S;Shrestha B;Radford J;Van Rooijen N;Campbell IL;King NJ
通讯作者：
King NJ
影响因子：
5.3
作者：
Liao, Bing;Zhao, Weihua;Beers, David R.;Henkel, Jenny S.;Appel, Stanley H.
通讯作者：
Appel, Stanley H.
影响因子：
6
作者：
Joly, Sandrine;Francke, Mike;Reme, Charlotte E.
通讯作者：
Reme, Charlotte E.
影响因子：
4.8
作者：
Maeda, Akiko;Maeda, Tadao;Palczewski, Krzysztof
通讯作者：
Palczewski, Krzysztof
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR