Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes
Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes
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DOI：
10.1016/s0002-9440(10)64036-9
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发表时间：
2001-03-01
影响因子：
6
通讯作者：
Libby, P
中科院分区：
文献类型：
--
作者：
Sugiyama, S;Okada, Y;Libby, P
炎症和氧化应激导致包括动脉粥样硬化在内的许多人类疾病的发病机制。晚期人类动脉粥样硬化包含高水平的酶髓过氧化物酶，其产生促氧化剂物质次氯酸（HOCl）。本研究记录了在导致急性冠状动脉综合征的侵蚀或破裂斑块中表达髓过氧化物酶的巨噬细胞数量增加。相比之下，人类脂肪条纹中的巨噬细胞含有很少或没有髓过氧化物酶。粒细胞巨噬细胞集落刺激因子，而不是巨噬细胞集落刺激因子，选择性地调节巨噬细胞表达髓过氧化物酶和产生HOCL的能力在体外。此外，髓过氧化物酶阳性的巨噬细胞斑块共定位与粒细胞巨噬细胞集落刺激因子。已知存在于人动脉粥样硬化斑块中的促炎刺激物，包括CD40配体、溶血磷脂酰胆碱或胆固醇晶体，可以诱导体外巨噬细胞从HOCl产生中释放髓过氧化物酶。HOCl修饰的蛋白质在人冠状动脉粥样硬化的破裂或侵蚀部位积累。这些结果确定了粒细胞巨噬细胞集落刺激因子作为人类动脉粥样硬化中巨噬细胞髓过氧化物酶表达的内源性调节因子，并支持髓过氧化物酶表达巨噬细胞在动脉粥样硬化并发症和急性冠状动脉综合征中的特定作用。
Inflammation and oxidative stress contribute to the pathogenesis of many human diseases including atherosclerosis. Advanced human atheroma contains high levels of the enzyme myeloperoxidase that produces the pro-oxidant species, hypochlorous acid (HOCl). This study documents increased numbers of myeloperoxidase-expressing macrophages in eroded or ruptured plaques causing acute coronary syndromes. In contrast, macrophages in human fatty streaks contain little or no myeloperoxidase. Granulocyte macrophage colony-stimulating factor, but not macrophage colony-stimulating factor, selectively regulates the ability of macrophages to express myeloperoxidase and produce HOCL in vitro. Moreover, myeloperoxidase-positive macrophages in plaques co-localized with granulocyte macrophage colony-stimulating factor. Pro-inflammatory stimuli known to be present in human atherosclerotic plaque, including CD40 ligand, lysophosphatidylcholine, or cholesterol crystals, could induce release of myeloperoxidase from HOCl production by macrophages in vitro. HOCl-modified proteins accumulated at ruptured or eroded sites of human coronary atheroma. These results identify granulocyte macrophage colony-stimulating factor as an endogenous regulator of macrophage myeloperoxidase expression in human atherosclerosis and support a particular role for the myeloperoxidase-expressing macrophages in atheroma complication and the acute coronary syndromes.