Calcium Oxalate Differentiates Human Monocytes Into Inflammatory M1 Macrophages.
Calcium Oxalate Differentiates Human Monocytes Into Inflammatory M1 Macrophages.
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DOI：
10.3389/fimmu.2018.01863
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发表时间：
2018
影响因子：
7.3
通讯作者：
Khan SR
中科院分区：
文献类型：
--
作者：
Dominguez-Gutierrez PR;Kusmartsev S;Canales BK;Khan SR
许多高草酸尿状态与肾脏中的草酸钙 (CaOx) 沉积有关。在结石病的动物模型中，这些晶体与作为先天免疫一部分迁移到肾脏的循环单核细胞相互作用。同样，排泄高水平草酸盐的患者肾脏中的巨噬细胞包围氧化钙晶体。我们研究了这种暴露的影响以及随后的体外人体免疫反应。原代人单核细胞取自健康供体，并暴露于 CaOx、草酸钾和草酸锌 (ZnOx)。使用多重 ELISA 测量细胞因子的产生。进行定量逆转录聚合酶链反应以验证 mRNA 表达谱。 M1巨噬细胞表型通过免疫荧光显微镜证实。原代单核细胞和 THP-1 细胞（一种人类单核细胞系）均以剂量依赖性方式对 CaOx 晶体产生强烈反应，产生 TNF-α、IL-1β、IL-8 和 IL-10 转录物。与单独的 LPS 相比，暴露于 CaOx 后 1 小时的 LPS 对细胞因子的产生具有累加效应，然而，LPS 后暴露于 CaOx 导致细胞因子的产生显着减少。取自单核细胞的上清液预先暴露于 CaOx 晶体，增强 M2 巨噬细胞晶体的吞噬作用。 CaOx（而非钾或 ZnOx）促进单核细胞分化为炎症性 M1 样巨噬细胞。在我们的体外实验中，人单核细胞被 CaOx 激活并产生炎症细胞因子。单核细胞通过特定机制识别 CaOx 晶体，可以增强或减弱对 LPS 的先天免疫反应。 CaOx 促进 M1 巨噬细胞发育。这些结果表明单核细胞在促进 CaOx 诱导的炎症中具有重要作用。
A number of hyperoxaluric states have been associated with calcium oxalate (CaOx) deposits in the kidneys. In animal models of stone disease, these crystals interact with circulating monocytes that have migrated into the kidney as part of innate immunity. Similarly, macrophages surround CaOx crystals in kidneys of patients excreting high levels of oxalate. We investigate the effect of this exposure and subsequent human immunological response in vitro. Primary human monocytes were collected from healthy donors and exposed to CaOx, potassium oxalate, and zinc oxalate (ZnOx). Cytokine production was measured with a multiplex ELISA. Quantitative reverse transcription-polymerase chain reaction was done to validate the mRNA profile expression. M1 macrophage phenotype was confirmed with immunofluorescence microscopy. Both primary monocytes and THP-1 cells, a human monocytic cell line, respond strongly to CaOx crystals in a dose-dependent manner producing TNF-α, IL-1β, IL-8, and IL-10 transcripts. Exposure to CaOx followed by 1 h with LPS had an additive effect for cytokine production compared to LPS alone, however, LPS followed by CaOx led to significant decrease in cytokine production. Supernatants taken from monocytes were previously exposed to CaOx crystals enhance M2 macrophage crystal phagocytosis. CaOx, but not potassium or ZnOx, promotes monocyte differentiation into inflammatory M1-like macrophages. In our in vitro experiment, human monocytes were activated by CaOx and produced inflammatory cytokines. Monocytes recognized CaOx crystals through a specific mechanism that can enhance or decrease the innate immune response to LPS. CaOx promoted M1 macrophage development. These results suggest that monocytes have an important role promoting CaOx-induced inflammation.
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影响因子：
19.6
作者：
Hoppe, B;Kemper, MJ;Langman, CB
通讯作者：
Langman, CB
DOI：
10.1016/j.juro.2015.11.048
发表时间：
2016-04
期刊：
The Journal of urology
影响因子：
--
作者：
Kusmartsev S;Dominguez-Gutierrez PR;Canales BK;Bird VG;Vieweg J;Khan SR
通讯作者：
Khan SR
影响因子：
19.6
作者：
Evan, Andrew P.;Lingeman, James E.;Worcester, Elaine M.;Bledsoe, Sharon B.;Sommer, Andre J.;Williams, James C., Jr.;Krambeck, Amy E.;Philips, Carrie L.;Coe, Fredric L.
通讯作者：
Coe, Fredric L.
DOI：
10.4049/jimmunol.1002311
发表时间：
2011-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Nahid MA;Satoh M;Chan EK
通讯作者：
Chan EK
DOI：
10.2147/ijnrd.s45466
发表时间：
2013-01-01
影响因子：
2
作者：
Cury, Ddia Bismara;Moss, Alan C.;Schor, Nestor
通讯作者：
Schor, Nestor