OxLDL or TLR2-induced cytokine response is enhanced by oxLDL-independent novel domain on mouse CD36.
OxLDL or TLR2-induced cytokine response is enhanced by oxLDL-independent novel domain on mouse CD36.
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DOI：
10.1016/j.imlet.2011.01.015
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发表时间：
2011-06-30
影响因子：
4.4
通讯作者：
Nagarajan, Shanmugam
中科院分区：
文献类型：
--
作者：
Xie, ChengHui;Ng, HangPong;Nagarajan, Shanmugam
氧化低密度脂蛋白与CD36结合导致巨噬细胞激活和泡沫细胞形成，这与动脉粥样硬化有关。然而，除了oxLDL外，CD36还可以诱导其他配体的炎症反应。在用抗CD36抗体阻断CD36 oxLDL结合功能的过程中，我们发现了CD36的一个新的结构域，它可以触发炎症反应--不依赖oxLDL结合。氧化低密度脂蛋白与小鼠报告细胞系RAW-Blue结合诱导肿瘤坏死因子-α和RANTES的基因和蛋白表达。用抗mCD36单抗JC63.1处理RAW-Blue细胞，JC63.1是一种激活的mCD36单抗，令人惊讶的是，它并没有抑制oxLDL诱导的反应。此外，这种抗体与CD36的结合单独在RAW-Blue细胞和原代小鼠巨噬细胞中诱导了促炎细胞因子反应。由于CD36−/−巨噬细胞不能诱导类似的反应，因此细胞因子反应的诱导仅对该抗体具有特异性，且依赖于CD36。抗CD36抗体的相互作用导致了核因子-κB和MAPK的激活。值得注意的是，CD36多肽阻止了oxLDL诱导的泡沫细胞形成和巨噬细胞激活。但CD36肽不能抑制mCD36单抗激活巨噬细胞的作用。此外，激活mCD36单抗可增强oxLDL、TLR2或TLR4介导的炎症反应。总之，我们的数据提供了证据，激活mCD36 mAb结合到一个不同于小鼠CD36上oxLDL结合结构域的结构域，并提示该结构域上的相互作用可能有助于导致oxLDL非依赖性巨噬细胞炎症反应，从而导致慢性炎症性疾病。
OxLDL binding to CD36 is shown to result in macrophage activation and foam cell formation that have been implicated in atherosclerosis. However, CD36 has also been shown to induce inflammatory response to other ligands besides oxLDL. During the course of blocking CD36 oxLDL binding function using anti CD36 antibodies, we have identified a novel domain of CD36 that triggers inflammatory response-independent of oxLDL binding. OxLDL bound to the mouse reporter cell line RAW-Blue induced TNF-α and RANTES mRNA and protein expression. Pretreatment of RAW-Blue cells with an anti-mCD36 mAb, JC63.1, an activating mCD36 mAb, surprisingly did not inhibit oxLDL-induced response. Further, binding of this antibody to CD36 alone induced a pro-inflammatory cytokine response in RAW-Blue cells as well as primary mouse macrophages. The induction of cytokine response was specific only to this antibody and was CD36-dependent, since CD36−/− macrophages failed to induce a similar response. The interaction of the antibody to CD36 led to activation of NF-κB and MAP kinase. Notably, a CD36 peptide blocked oxLDL-induced foam cell formation and macrophage activation. However, the activating mCD36 mAb induced macrophage activation was not inhibited by CD36 peptide. Further, activating mCD36 mAb enhanced oxLDL- or TLR2- or TLR4-mediated inflammatory responses. Collectively, our data provide evidence that activating mCD36 mAb binds to a domain different from the oxLDL-binding domain on mouse CD36, and suggest that interaction at this domain may contribute to oxLDL-independent macrophage inflammatory responses that lead to chronic inflammatory diseases.
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影响因子：
64.8
作者：
Hoebe, K;Georgel, P;Beutler, B
通讯作者：
Beutler, B
CD36介导了对β-淀粉样蛋白的先天宿主反应。
影响因子：
15.3
作者：
El Khoury, JB;Moore, KJ;Means, TK;Leung, J;Terada, K;Toft, M;Freeman, MW;Luster, AD
通讯作者：
Luster, AD
影响因子：
3.7
作者：
Jimenez-Dalmaroni MJ;Xiao N;Corper AL;Verdino P;Ainge GD;Larsen DS;Painter GF;Rudd PM;Dwek RA;Hoebe K;Beutler B;Wilson IA
通讯作者：
Wilson IA
影响因子：
15.9
作者：
Febbraio, M;Podrez, EA;Silverstein, RL
通讯作者：
Silverstein, RL
影响因子：
6.4
作者：
Crandall, I;Guy, RA;Kain, KC
通讯作者：
Kain, KC