Acosta-Pérez G, Maximina Bertha Moreno-Altamirano M, Rodríguez-Luna G, Javier Sánchez-Garcia F
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico DF, Mexico.
Scand J Immunol. 2008 Oct;68(4):423-9. doi: 10.1111/j.1365-3083.2008.02155.x.
Monocytes and macrophages may encounter both pro-inflammatory and anti-inflammatory signals during their lifetime, in the form of micro-organisms or their products or as cytokines. In addition, macrophages are also exposed to apoptotic and necrotic cells. Apoptosis or 'programmed cell death' is thought to be the physiological end of developing or maturing cells, whereas necrosis is regarded as 'accidental death' or injury-associated cell death. Apoptotic cells are cleared from tissues by phagocytic cells without eliciting an inflammatory response, while necrotic cells elicit inflammation. Several cell membrane molecules from apoptotic and necrotic, as well as from phagocytic cells, have been shown to participate in the process of endocytosis of dying and potentially harmful cells. Apart from an array of cell surface receptors, it is also known that lipid rafts are key components of cell-cell communication and signalling. By using the interaction of BALB/c mice thymus-derived apoptotic or necrotic cells with murine macrophages of the J774 cell line as a model system, we provide evidence that endocytosis of apoptotic but not of necrotic cells is inhibited by methyl-beta-cyclodextrin, a cholesterol sequestering agent, able to disrupt lipid rafts. However, necrotic but not apoptotic cells co-localize with lipid rafts within macrophages. Interestingly, necrotic cell-induced secretion of TNF-alpha and IL-1beta was also inhibited by methyl-beta-cyclodextrin, thus suggesting a role for lipid rafts in the signalling of this particular inflammatory response. Taken together, our results argue in favour of differential macrophage recognition of apoptotic and necrotic cells at the level of lipid rafts, and endocytosis versus signalling for TNF-alpha and IL-1beta synthesis.
单核细胞和巨噬细胞在其生命周期中可能会遇到促炎和抗炎信号，这些信号以微生物或其产物的形式存在，或者以细胞因子的形式存在。此外，巨噬细胞还会接触凋亡细胞和坏死细胞。凋亡或“程序性细胞死亡”被认为是发育或成熟细胞的生理性终点，而坏死则被视为“意外死亡”或与损伤相关的细胞死亡。凋亡细胞通过吞噬细胞从组织中清除，不会引发炎症反应，而坏死细胞则会引发炎症。已经证明，来自凋亡细胞、坏死细胞以及吞噬细胞的几种细胞膜分子参与了对濒死和潜在有害细胞的内吞过程。除了一系列细胞表面受体外，还已知脂筏是细胞间通讯和信号传导的关键组成部分。通过使用BALB/c小鼠胸腺来源的凋亡或坏死细胞与J774细胞系的小鼠巨噬细胞之间的相互作用作为模型系统，我们提供了证据表明，甲基-β-环糊精（一种能够破坏脂筏的胆固醇螯合剂）可抑制凋亡细胞而非坏死细胞的内吞作用。然而，坏死细胞而非凋亡细胞与巨噬细胞内的脂筏共定位。有趣的是，甲基-β-环糊精也抑制了坏死细胞诱导的TNF-α和IL-1β的分泌，因此表明脂筏在这种特定炎症反应的信号传导中发挥作用。综上所述，我们的结果支持巨噬细胞在脂筏水平上对凋亡细胞和坏死细胞的差异性识别，以及内吞作用与TNF-α和IL-1β合成信号传导之间的差异。
