Anti-phosphorylcholine-opsonized low-density lipoprotein promotes rapid production of proinflammatory cytokines by dendritic cells and natural killer cells.
Anti-phosphorylcholine-opsonized low-density lipoprotein promotes rapid production of proinflammatory cytokines by dendritic cells and natural killer cells.
复制标题
抗磷酸胆碱调理低密度脂蛋白促进树突状细胞和自然杀伤细胞快速产生促炎细胞因子。
DOI：
10.1111/j.1600-0765.2010.01292.x
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发表时间：
2010
影响因子：
3.5
通讯作者：
Tew,JG
中科院分区：
文献类型：
--
作者：
Kikuchi,T;ElShikh,MM;ElSayed,RM;Purkall,DB;Elaasser,MM;Sarraf,A;Barbour,SE;Schenkein,HA;Tew,JG
菊池T，El Shikh MM，El Sayed RM，Purkall DB，Elaasser MM，Sarraf A，Barthaline SE，Schenkein HA，Tew JG.抗磷酸胆碱调理的低密度脂蛋白促进树突状细胞和自然杀伤细胞快速产生促炎细胞因子。J Periodont Res 2010; 45：720-730.© 2010 John Wiley & Sons A/S背景和目的：流行病学和动物研究表明，牙周感染会增加动脉粥样硬化的风险。牙周炎患者的抗磷酸胆碱（anti-PC）水平升高，不仅与许多牙周微生物反应，还与最低修饰低密度脂蛋白（mmLDL）反应。树突状细胞（DC）存在于动脉壁中并在动脉粥样硬化病变中积聚。抗PC结合mmLDL的能力提示了这样一种假设，即调理的mmLDL将刺激DCs并增强促炎细胞因子的产生，从而促进动脉粥样硬化斑块的发展。材料和方法：使用粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素（IL）-4产生单核细胞衍生的DCs（mDCs），然后用mmLDL或用抗PC调理的mmLDL刺激。使用流式细胞术、共聚焦显微镜和细胞因子测定确定抗PC效应。结果：经mmLDL刺激后，DC表达少量CD 83，产生少量IL-12 p70。然而，抗PC调理的mmLDL增强了DC成熟，如CD 83上调和IL-12 p70快速（≤ 48 h）产生所示（如果有干扰素-γ（IFN-γ）来源）。 在白细胞培养物中，自然杀伤（NK）细胞在与抗PC调理的mmLDL激活的产生IL-12的DC相互作用时快速产生IFN-γ（≤48 h）。 结论：最小修饰LDL刺激的DC和NK细胞是相互刺激的，DC IL-12 p70和NK细胞IFN-γ分别为NK细胞和DC所需。此外，当LDL被抗PC调理时，这些促炎细胞因子的产生显著增强。简而言之，数据表明牙周炎患者抗PC水平升高可能会促进动脉粥样硬化的机制。
Kikuchi T, El Shikh MM, El Sayed RM, Purkall DB, Elaasser MM, Sarraf A, Barbour SE, Schenkein HA, Tew JG. Anti‐phosphorylcholine opsonized low‐density lipoprotein promotes rapid production of proinflammatory cytokines by dendritic cells and natural killer cells. J Periodont Res 2010; 45: 720–730. © 2010 John Wiley & Sons A/SBackground and Objective:Epidemiological and animal studies suggest that periodontal infections increase atherosclerosis risk. Periodontitis patients have elevated levels of anti‐phosphorylcholine (anti‐PC) reactive not only with numerous periodontal organisms but also with minimally modified low‐density lipoprotein (mmLDL). Dendritic cells (DCs) reside in arterial walls and accumulate in atherosclerotic lesions. The ability of anti‐PC to bind mmLDL prompted the hypothesis that opsonized mmLDL would stimulate DCs and enhance the production of proinflammatory cytokines that promote atherogenic plaque development.Material and Methods:Monocyte‐derived DCs (mDCs) were generated using granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and interleukin (IL)‐4, then stimulated with mmLDL or with anti‐PC‐opsonized mmLDL. The anti‐PC effect was determined using flow cytometry, cofocal microscopy and cytokine assays. The production of CD83, IL‐12p35 mRNA, IL‐12p40 mRNA, IL‐12p70 and IL‐10 by DCs was monitored.Results:Dendritic cells stimulated with mmLDL expressed little CD83 and produced little IL‐12p70. However, anti‐PC‐opsonized mmLDL enhanced DC maturation, as indicated by upregulated CD83 and rapid (≤ 48 h) production of IL‐12p70 if a source of interferon‐γ (IFN‐γ) was available. In leukocyte cultures, natural killer (NK) cells rapidly produced IFN‐γ (≤ 48 h) when interacting with IL‐12‐producing DCs activated by anti‐PC‐opsonized mmLDL. Moreover, IFN‐γ promoted DC IL‐12 responses that were further augmented when mmLDL was opsonized with anti‐PC.Conclusion:Minimally modified LDL‐stimulated DCs and NK cells were mutually stimulatory, with DC IL‐12p70 needed by NK cells and with NK cell IFN‐γ needed by DCs. Moreover, production of these proinflammatory cytokines was markedly enhanced when LDL was opsonized by anti‐PC. In short, the data suggest that the elevated anti‐PC levels in periodontitis patients could promote a mechanism that facilitates atherosclerosis.