Kaartinen M, Penttilä A, Kovanen P T
Wihuri Research Institute, Helsinki, Finland.
Arterioscler Thromb Vasc Biol. 1995 Nov;15(11):2047-54. doi: 10.1161/01.atv.15.11.2047.
In experimental studies in vitro, mast cells have induced uptake of apolipoprotein B-100 (apoB-100)-containing low-density lipoproteins by macrophages, with the subsequent formation of foam cells, the hallmarks of atherosclerosis. Recently, increased numbers of activated, ie, degranulated, mast cells were found to be present in human coronary fatty streaks and atheromas. We therefore sought evidence of a connection between mast cells and foam cell formation in vivo. In electron microscopic studies of human aortic and coronary fatty streaks and atheromas, exocytosed cytoplasmic secretory granules of mast cells were detected in the vicinity of their parent cells. These exocytosed granules had bound apoB-100-containing lipoproteins, as indicated by their positive staining with MB 47, a monoclonal antibody against apoB-100. A smooth muscle cell was observed to be in the process of phagocytosing one such exocytosed granule, and in the vicinity of a degranulated mast cell a foam cell contained an ingested mast cell granule. Therefore, the micrographs show that exocytosed granules of intimal mast cells may contribute to intimal foam cell formation and suggest a role for mast cells in human atherogenesis. More generally, the findings provide evidence that phagocytosis of apoB-100-carrying particles is one mechanism by which lipoproteins enter human arterial intimal cells.
在体外实验研究中,肥大细胞可诱导巨噬细胞摄取含载脂蛋白B-100(apoB-100)的低密度脂蛋白,随后形成泡沫细胞,这是动脉粥样硬化的特征。最近发现,在人类冠状动脉脂肪条纹和动脉粥样斑块中,活化的(即脱颗粒的)肥大细胞数量增加。因此,我们试图寻找肥大细胞与体内泡沫细胞形成之间存在联系的证据。在对人类主动脉和冠状动脉脂肪条纹及动脉粥样斑块进行的电子显微镜研究中,在肥大细胞母细胞附近检测到了其胞吐的细胞质分泌颗粒。这些胞吐颗粒结合了含apoB-100的脂蛋白,用抗apoB-100单克隆抗体MB 47进行阳性染色可证明这一点。观察到一个平滑肌细胞正在吞噬一个这样的胞吐颗粒,并且在一个脱颗粒的肥大细胞附近,一个泡沫细胞含有一个摄取的肥大细胞颗粒。因此,显微照片显示内膜肥大细胞的胞吐颗粒可能有助于内膜泡沫细胞的形成,并提示肥大细胞在人类动脉粥样硬化发生过程中发挥作用。更普遍地说,这些发现提供了证据,表明吞噬携带apoB-100的颗粒是脂蛋白进入人类动脉内膜细胞的一种机制。