Receptor-independent fluid-phase pinocytosis mechanisms for induction of foam cell formation with native low-density lipoprotein particles.
Receptor-independent fluid-phase pinocytosis mechanisms for induction of foam cell formation with native low-density lipoprotein particles.
复制标题
非本地低密度脂蛋白颗粒诱导泡沫细胞形成的受体非依赖性流体性胞毒性机制。
DOI：
10.1097/mol.0b013e32834adadb
复制
发表时间：
2011-10
影响因子：
4.4
通讯作者：
Kruth HS
中科院分区：
文献类型：
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作者：
Kruth HS
由于早期研究结果表明，天然低密度脂蛋白 (LDL) 在体外培养过程中并未显着增加巨噬细胞胆固醇含量，因此研究人员推测 LDL 必须以某种方式进行修饰才能触发巨噬细胞对其的摄取。本综述的目的是讨论最近的研究结果，这些发现表明天然未修饰的 LDL 可以诱导大量巨噬细胞胆固醇积累，模仿动脉粥样硬化斑块内发生的巨噬细胞泡沫细胞形成。显示出高速率液相胞饮作用的巨噬细胞也显示出通过大胞饮体和微胞饮体内非受体介导的摄取对天然未修饰的LDL的类似高摄取率。巨噬细胞对 LDL 的非饱和液相摄取将巨噬细胞转化为泡沫细胞。不同的巨噬细胞表型表现出组成型液相胞饮作用或诱导型液相胞饮作用。小鼠动脉粥样硬化斑块内的巨噬细胞已证实了流体相胞饮作用，表明该途径有助于斑块巨噬细胞胆固醇积累。与之前的看法相反，巨噬细胞可以通过不依赖于受体的液相胞饮作用将这些巨噬细胞转化为泡沫细胞，从而摄取大量天然未修饰的 LDL。因此，在研究限制动脉粥样硬化斑块中巨噬细胞胆固醇积累的策略时，应考虑针对巨噬细胞液相胞饮作用。
Because early findings indicated that native low density lipoprotein (LDL) did not substantially increase macrophage cholesterol content during in vitro incubations, investigators presumed that LDL must be modified in some way to trigger its uptake by the macrophage. The purpose of this review is to discuss recent findings showing that native unmodified LDL can induce massive macrophage cholesterol accumulation mimicking macrophage foam cell formation that occurs within atherosclerotic plaques. Macrophages that show high rates of fluid-phase pinocytosis also show similar high rates of uptake of native unmodified LDL through non-receptor mediated uptake within both macropinosomes and micropinosomes. Non-saturable fluid-phase uptake of LDL by macrophages converts the macrophages into foam cells. Different macrophage phenotypes demonstrate either constitutive fluid-phase pinocytosis or inducible fluid-phase pinocytosis. Fluid-phase pinocytosis has been demonstrated by macrophages within mouse atherosclerotic plaques indicating that this pathway contributes to plaque macrophage cholesterol accumulation. Contrary to what has been believed previously, macrophages can take up large amounts of native unmodified LDL by receptor-independent, fluid-phase pinocytosis converting these macrophages into foam cells. Thus, targeting macrophage fluid-phase pinocytosis should be considered when investigating strategies to limit macrophage cholesterol accumulation in atherosclerotic plaques.