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摘要 : Nicholas Leeper及同事表明,小鼠和人类的动脉粥样硬化病变发出“别吃我”信号—通过抗吞噬跨膜蛋白CD47的表达 — 阻止病变组织的有效移除。

 Nicholas Leeper及同事表明,小鼠和人类的动脉粥样硬化病变发出“别吃我”信号—通过抗吞噬跨膜蛋白CD47的表达 — 阻止病变组织的有效移除。他们表明,在一些动脉粥样硬化小鼠模型中,施用抗CD47抗体能使出错的吞噬清除作用(或胞葬作用)恢复正常,带来积极的结果。这些结果表明,靶向胞葬促进疗法可能有治疗心血管疾病的潜力。


CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis


Atherosclerosis is the disease process that underlies heart attack and stroke1. Advanced lesions at risk of rupture are characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular debris2. Why these cells are not cleared remains unknown3. Here we show that atherogenesis is associated with upregulation of CD47, a key anti-phagocytic molecule that is known to render malignant cells resistant to programmed cell removal, or ‘efferocytosis’4, 5, 6, 7. We find that administration of CD47-blocking antibodies reverses this defect in efferocytosis, normalizes the clearance of diseased vascular tissue, and ameliorates atherosclerosis in multiple mouse models. Mechanistic studies implicate the pro-atherosclerotic factor TNF-α as a fundamental driver of impaired programmed cell removal, explaining why this process is compromised in vascular disease. Similar to recent observations in cancer5, impaired efferocytosis appears to play a pathogenic role in cardiovascular disease, but is not a fixed defect and may represent a novel therapeutic target.

来源: Nature 浏览次数:1


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