CD36 调节抗中性粒细胞胞质抗体血管炎中的巨噬细胞和内皮细胞激活以及多核巨细胞形成。
CD36 regulates macrophage and endothelial cell activation and multinucleate giant cell formation in anti neutrophil cytoplasm antibody vasculitis.
机构信息
UCL Centre for Kidney and Bladder Health, Royal Free Hospital, London, UK.
Institute of Immunology and Immunotherapy, College of Medical & Dental Sciences University of Birmingham, Birmingham, UK.
出版信息
Clin Immunol. 2024 Mar;260:109914. doi: 10.1016/j.clim.2024.109914. Epub 2024 Jan 27.
OBJECTIVE
To investigate CD36 in ANCA-associated vasculitis (AAV), a condition characterized by monocyte/macrophage activation and vascular damage.
METHODS
CD36 expression was assessed in AAV patients and healthy controls (HC). The impact of palmitic acid (PA) stimulation on multinucleate giant cell (MNGC) formation, macrophage, and endothelial cell activation, with or without CD36 knockdown, was examined.
RESULTS
CD36 was overexpressed on AAV patients' monocytes compared to HC, regardless of disease activity. AAV patients exhibited elevated soluble CD36 levels in serum and plasma and PR3-ANCA patients' monocytes demonstrated increased MNGC formation following PA stimulation compared to HC. PA stimulation of macrophages or endothelial cells resulted in heightened CD36 expression, cell activation, increased macrophage migration inhibitory factor (MIF) production, and c-Myc expression, with attenuation upon CD36 knockdown.
CONCLUSION
CD36 participates in macrophage and endothelial cell activation and MNGC formation, features of AAV pathogenesis. AAV treatment may involve targeting CD36 or MIF.
目的
研究 CD36 在抗中性粒细胞胞浆抗体相关性血管炎（AAV）中的作用，AAV 以单核细胞/巨噬细胞活化和血管损伤为特征。
方法
评估了 AAV 患者和健康对照者（HC）的 CD36 表达。检测了棕榈酸（PA）刺激对多核巨细胞（MNGC）形成、巨噬细胞和内皮细胞活化的影响，以及是否存在 CD36 敲低。
结果
与 HC 相比，AAV 患者的单核细胞上 CD36 过度表达，无论疾病活动如何。AAV 患者血清和血浆中可溶性 CD36 水平升高，与 HC 相比，PR3-ANCA 患者的单核细胞在 PA 刺激后形成更多的 MNGC。PA 刺激巨噬细胞或内皮细胞导致 CD36 表达、细胞活化、增加巨噬细胞迁移抑制因子（MIF）产生和 c-Myc 表达增加，而 CD36 敲低则减弱了这些反应。
结论
CD36 参与了巨噬细胞和内皮细胞的活化以及 MNGC 的形成，这是 AAV 发病机制的特征。AAV 的治疗可能涉及靶向 CD36 或 MIF。
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