Rohm Ilonka, Sattler Sandra, Atiskova Yevgeniya, Kretzschmar Daniel, Pistulli Rudin, Franz Marcus, Jung Christian, Mall Gita, Kronert Thomas, Schulze Paul C, Yilmaz Atilla
Clin Lab. 2016 Dec 1;62(12):2293-2303. doi: 10.7754/Clin.Lab.2016.160517.
Atherosclerosis is an inflammatory disease of the vessel wall promoted by different immune cells and inflammatory mediators.
In this study, 26 human plaques and 12 control vessels without atherosclerosis were immunohistochemically stained to analyze the emergence of mast cells dependent on plaque morphology and to correlate mast cell occurrence with the emergence of myeloid as well as plasmacytoid dendritic cells. Also, mast cell emergence was correlated with the number of pro-inflammatory T cells. For this, plaques were classified as stable or unstable according to established histological criteria.
As expected, atherosclerotic lesions showed significantly higher numbers of tryptase+, chymase+, and cathepsin G+ mast cells compared to control vessels, particularly in lesions with unstable morphology. As a novel finding, we detected significant correlations between mast cells and myeloid dendritic cells (fascin, CD83, r > 0.3, p < 0.01), but not plasmacytoid dendritic cells (CD123, CD304). Also, we observed significant correlations of mast cells and different subgroups of pro-inflammatory T cells (CD3, CD8, CD161, CD25; r > 0.35, p < 0.05).
Overall, the higher number of mast cells in plaques, particularly with unstable morphology, suggests that mast cells might be involved in the progression of atherosclerosis. The correlation of mast cells with other immune cells that are pivotal in atherogenesis, e.g., myeloid dendritic cells and pro-inflammatory T cells, also suggests an interplay leading to plaque destabilization. Therefore, modulating local mast cell function and invasion into the plaque might be a therapeutic tool for plaque stabilization.
动脉粥样硬化是一种血管壁炎症性疾病，由不同的免疫细胞和炎症介质促成。
在本研究中，对26个人类斑块和12个无动脉粥样硬化的对照血管进行免疫组织化学染色，以分析依赖于斑块形态的肥大细胞出现情况，并将肥大细胞的出现与髓样及浆细胞样树突状细胞的出现相关联。此外，肥大细胞的出现与促炎性T细胞数量相关。为此，根据既定的组织学标准将斑块分类为稳定或不稳定。
正如预期的那样，与对照血管相比，动脉粥样硬化病变显示出明显更多的色氨酸酶阳性、糜蛋白酶阳性和组织蛋白酶G阳性肥大细胞，特别是在形态不稳定的病变中。作为一项新发现，我们检测到肥大细胞与髓样树突状细胞（肌动蛋白、CD83，r>0.3，p<0.01）之间存在显著相关性，但与浆细胞样树突状细胞（CD123、CD304）无相关性。此外，我们观察到肥大细胞与促炎性T细胞的不同亚组（CD3、CD8、CD161、CD25；r>0.35，p<0.05）之间存在显著相关性。
总体而言，斑块中肥大细胞数量较多，特别是形态不稳定的斑块，表明肥大细胞可能参与动脉粥样硬化的进展。肥大细胞与动脉粥样硬化发生过程中起关键作用的其他免疫细胞（如髓样树突状细胞和促炎性T细胞）之间的相关性也表明存在导致斑块不稳定的相互作用。因此，调节局部肥大细胞功能并使其侵入斑块可能是稳定斑块的一种治疗手段。
