Kokkonen J O, Kovanen P T
Wihuri Research Institute, Helsinki, Finland.
Eur Heart J. 1990 Aug;11 Suppl E:134-46. doi: 10.1093/eurheartj/11.suppl_e.134.
Rat serosal mast cells contain secretory granules composed of a heparin proteoglycan matrix in which neutral proteases are embedded. Stimulation of the mast cells leads to granule exocytosis and formation of two pools of granules located extracellularly, firstly, granules expelled into the 'free' extracellular space and ultimately phagocytosed by the scavenging cells in the vicinity of mast cells and, secondly, granules which remain associated with their parent mast cells, and become internalized by them during recovery from stimulation. If mast cells are stimulated in the presence of macrophages in a low density lipoprotein (LDL)-containing medium, LDL is bound to the heparin proteoglycan component of the exocytosed granules whether they are expelled into the 'free' extracellular space or remain associated with the mast cells. The granules located in the 'free' extracellular space degrade, by the action of their neutral proteases, the apolipoprotein B component of the bound LDL. The proteolytic degradation of the granule-bound LDL results in its modification such that large fused LDL particles are formed on the granule surface. Phagocytosis, by macrophages, of the granules containing fused LDL particles leads to lysosomal degradation of LDL and cholesterol accumulation in macrophages as non-membrane-bound cholesteryl ester droplets, typical of foam cells. In contrast, the rapid internalization of the LDL-bearing, mast-cell-associated granules by recovering mast cells is not followed by lysosomal processing of LDL. Instead, it leads to cholesterol accumulation in mast cells, in the form of large, partially degraded, modified LDL particles, in the granule compartment.
大鼠浆膜肥大细胞含有由肝素蛋白聚糖基质组成的分泌颗粒，其中嵌入了中性蛋白酶。肥大细胞的刺激导致颗粒胞吐，并在细胞外形成两群颗粒，首先，颗粒被排入“游离”细胞外空间，最终被肥大细胞附近的清除细胞吞噬；其次，颗粒仍与其母肥大细胞相关，并在从刺激中恢复过程中被其内化。如果在含有低密度脂蛋白（LDL）的培养基中，在巨噬细胞存在的情况下刺激肥大细胞，LDL会与胞吐颗粒的肝素蛋白聚糖成分结合，无论这些颗粒是被排入“游离”细胞外空间还是仍与肥大细胞相关。位于“游离”细胞外空间的颗粒通过其中性蛋白酶的作用，降解结合的LDL的载脂蛋白B成分。颗粒结合的LDL的蛋白水解降解导致其发生修饰，从而在颗粒表面形成大的融合LDL颗粒。巨噬细胞吞噬含有融合LDL颗粒的颗粒会导致LDL的溶酶体降解以及胆固醇以非膜结合胆固醇酯滴的形式在巨噬细胞中积累，这是泡沫细胞的典型特征。相比之下，恢复中的肥大细胞对携带LDL的肥大细胞相关颗粒的快速内化并不会随后对LDL进行溶酶体处理。相反，它会导致胆固醇以大的、部分降解的、修饰的LDL颗粒的形式在肥大细胞的颗粒区室中积累。
