Wihuri Research Institute, Kalliolinnantie 4, FI-00140 Helsinki, Finland.
Atherosclerosis. 2011 Feb;214(2):357-63. doi: 10.1016/j.atherosclerosis.2010.11.024. Epub 2010 Nov 26.
Human atherosclerotic lesions contain mast cells and immunoglobulin G immune complexes containing oxidized low-density lipoproteins (oxLDL-IgG ICs). Here we studied whether such oxLDL-IgG ICs can activate human mast cells and induce them to express and secrete pro-inflammatory cytokines that are potentially capable of inducing and amplifying atherogenic processes.
Incubation of cultured human mast cells in the presence of oxLDL-IgG ICs led to a significant dose-dependent upregulation of the expression and secretion of tumor necrosis factor-alpha (TNF-a) and interleukin-8 (IL-8), and the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1). The secretory responses were dose-dependent and associated with moderate release of histamine and tryptase, which are preformed mast cell mediators contained in the cytoplasmic secretory granules of the cells. Also native LDL-IgG ICs induced similar pro-inflammatory cytokine response, suggesting that ICs per se are important for the IgG IC-induced mast cell activation.
Mast cells in atherosclerotic lesions which also contain oxLDL-IgG ICs may become activated by the ICs and secrete many pro-inflammatory cytokines. Our results suggest that intimal mast cells act as a cellular link between oxLDL-IgG ICs and the inflammatory response in atherosclerosis.
人动脉粥样硬化病变中含有肥大细胞和含有氧化型低密度脂蛋白（oxLDL）的免疫球蛋白 G 免疫复合物（oxLDL-IgG ICs）。在这里，我们研究了这种 oxLDL-IgG IC 是否可以激活人肥大细胞，并诱导其表达和分泌潜在的促炎细胞因子，从而诱导和放大动脉粥样硬化过程。
在存在 oxLDL-IgG IC 的情况下孵育培养的人肥大细胞，导致肿瘤坏死因子-α（TNF-α）和白细胞介素-8（IL-8）以及趋化细胞因子单核细胞趋化蛋白-1（MCP-1）的表达和分泌呈显著的剂量依赖性上调。分泌反应呈剂量依赖性，与组胺和类胰蛋白酶的适度释放有关，组胺和类胰蛋白酶是细胞浆分泌颗粒中预先存在的肥大细胞介质。天然 LDL-IgG IC 也诱导了类似的促炎细胞因子反应，表明 IC 本身对于 IgG IC 诱导的肥大细胞激活很重要。
动脉粥样硬化病变中的肥大细胞也含有 oxLDL-IgG ICs，这些肥大细胞可能被 IC 激活并分泌许多促炎细胞因子。我们的结果表明，内膜肥大细胞作为 oxLDL-IgG ICs 和动脉粥样硬化炎症反应之间的细胞连接。
