Oxidized LDL activated eosinophil polarize macrophage phenotype from M2 to M1 through activation of CD36 scavenger receptor.
Oxidized LDL activated eosinophil polarize macrophage phenotype from M2 to M1 through activation of CD36 scavenger receptor.
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DOI：
10.1016/j.atherosclerosis.2017.05.011
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发表时间：
2017-08
期刊：
影响因子：
5.3
通讯作者：
Sharifi BG
中科院分区：
文献类型：
--
作者：
Qin M;Wang L;Li F;Yang M;Song L;Tian F;Yukht A;Shah PK;Rothenberg ME;Sharifi BG
炎症，特别是先天免疫，在心血管疾病中起着重要作用。这项研究的目的是调查是否动脉粥样硬化的决定因素，如氧化LDL调节嗜酸性粒细胞的表型。用氧化LDL处理培养的嗜酸性粒细胞，测定选择性炎症和抗炎细胞因子的表达。此外，还鉴定了介导这些事件的嗜酸性粒细胞受体和信号。用氧化LDL （Ox-LDL）处理培养的嗜酸性粒细胞特异性诱导IFNα和IFNβ的表达，而不影响其他促炎细胞因子如TNFα、IL-1β和IL-6的表达。在巨噬细胞中，Ox-LDL下调IFNα和IFNβ的表达，表明Ox-LDL对I型干扰素表达的影响是嗜酸性粒细胞特异性的。此外，我们注意到嗜酸性细胞组成性地表达IL-4和IL-13，而Ox-LDL显著下调它们的表达。Ox-LDL信号分析显示，嗜酸性粒细胞组成性表达SRB2、CD36和CD68清除率受体，Ox-LDL显著诱导CD36的表达。通过siRNA和中和抗体对CD36信号的进一步分析表明，Ox-LDL诱导I型IFN是由CD36信号介导的，而IL-4的下调不依赖于CD36的激活。我们进一步发现，用Ox-LDL处理的嗜酸性粒细胞收集的条件培养基处理的腹膜巨噬细胞显著诱导M1标记物如iNOS、IL6、SOSC3和TNFα的表达；而未处理的嗜酸性粒细胞条件培养基显著诱导M2标记物如ARG1和CCL24的表达。我们的数据表明，动脉粥样硬化可以激活嗜酸性粒细胞并调节巨噬细胞的表型（从M2表型到M1表型），部分是通过CD36受体信号传导。
Inflammation, particularly innate immunity, play an important role in cardiovascular diseases. The aim of this study was to investigate whether atherogenic determinants such as oxidized LDL modulate the phenotype of eosinophils. Cultured eosinophils were treated with oxidized LDL and the expression of selective inflammatory and anti-inflammatory cytokines was determined. In addition, the eosinophil receptor and signaling that mediates these events were identified. Treatment of cultured eosinophils with oxidized LDL (Ox-LDL) specifically induced the expression of IFNα and IFNβ without affecting expression of other proinflammatory cytokines, such as TNFα, IL-1β, and IL-6. In macrophages, Ox-LDL downregulated expression of both IFNα and IFNβ, suggesting that the effect of Ox-LDL on the expression of type I interferons is specific to eosinophils. Furthermore, we noted that eosinophils constitutively expressed IL-4 and IL-13, and Ox-LDL markedly downregulated their expression. Analysis of Ox-LDL signaling revealed that eosinophils constitutively expressed SRB2, CD36, and CD68 scavenger receptors, and Ox-LDL markedly induced the expression of CD36. Further analysis of CD36 signaling by siRNA and neutralizing antibodies showed that the induction of type I IFN by Ox-LDL is mediated by CD36 signaling whereas downregulation of IL-4 is independent of CD36 activation. We further showed that peritoneal macrophages treated with condition medium collected from Ox-LDL treated eosinophils markedly induced the expression of M1 markers such as iNOS, IL6, SOSC3 and TNFα; whereas the condition medium from non-treated eosinophils significantly induced expression of M2 markers like ARG1 and CCL24. Our data suggest that an atherogenic condition could activate eosinophils and modulate the phenotype of macrophages (from M2 to M1 phenotype), in part, through the CD36 receptor signaling.
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影响因子：
11.8
作者：
Heit, Bryan;Kim, Hani;Cosio, Gabriela;Castano, Diana;Collins, Richard;Lowell, Clifford A.;Kain, Kevin C.;Trimble, William S.;Grinstein, Sergio
通讯作者：
Grinstein, Sergio
影响因子：
4.8
作者：
RIGOTTI, A;ACTON, SL;KRIEGER, M
通讯作者：
KRIEGER, M
影响因子：
6
作者：
Coraci, IS;Husemann, J;El Khoury, JB
通讯作者：
El Khoury, JB
影响因子：
30.8
作者：
Gudbjartsson, Daniel F.;Bjornsdottir, Unnur S.;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
5
作者：
PRENTICE, RL;SZATROWSKI, TP;HAMILTON, HH
通讯作者：
HAMILTON, HH