Jones N L, Jerome W G, Lewis J C
Department of Pathology, Bouman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157-1092.
Am J Pathol. 1991 Aug;139(2):383-92.
Lysosomes have long been implicated as a factor contributing to the progression and complication of atherosclerosis. The authors' laboratory previously has shown that lysosomal ultrastructure in arterial macrophage foam cells is altered as primary lysosomes give rise to large pleiomorphic organelles on lipid accumulation during lesion progression. To further explore the subcellular alterations in lysosomes and associated organelles during foam cell formation, three-dimensional (3D) intermediate voltage electron microscopy was used to examine monocyte-derived macrophages (monocyte/macrophages) during early in vitro uptake of beta migrating very-low-density lipoproteins (beta VLDL). Lysosomes were identified using acid phosphatase cytochemistry, and in control cells these organelles constituted 3.5% of the total cytoplasmic volume. Both primary and secondary lysosomes were observed. Upon beta VLDL uptake, the total volume of acid-phosphatase-positive organelles increased threefold over 30 minutes, and the reaction product was found in three additional morphologically distinct structures: tubular lysosomes, membrane stacks, and endoplasmic reticulum with widened cisternae. The proportion of the cell occupied by each of the five acid-phosphatase-positive organelles was quantitated at 10 minutes, 30 minutes, 1 hour, and 4 hours of beta VLDL incubation, and their relative abundance was compared with controls that were processed either with no lipoprotein challenge or albumin incubation for 1 hour. Secondary lysosomes compartment volume peaked at 30 minutes; over the ensuing 3.5 hours, however, the reaction progressively shifted to three new membrane-limited locations. Our observations document the complex 3D organization and spacial relationships among the acid-phosphatase-positive structures induced by lipoprotein uptake. The 3D organization patterns for acid-phosphatase-positive lysosomes in lipoprotein-stimulated pigeon monocyte/macrophages were similar in several aspects to the complex lysosomes previously observed in the macrophages of pigeon arterial lesions.
长期以来，溶酶体一直被认为是促成动脉粥样硬化进展和并发症的一个因素。作者所在实验室先前已表明，在病变进展过程中，随着原发性溶酶体在脂质蓄积时产生大型多形性细胞器，动脉巨噬细胞泡沫细胞中的溶酶体超微结构会发生改变。为了进一步探究泡沫细胞形成过程中溶酶体及相关细胞器的亚细胞改变，利用三维（3D）中压电子显微镜检查了单核细胞衍生的巨噬细胞（单核细胞/巨噬细胞）在体外早期摄取β迁移极低密度脂蛋白（β-VLDL）的过程。通过酸性磷酸酶细胞化学鉴定溶酶体，在对照细胞中，这些细胞器占细胞质总体积的3.5%。同时观察到了原发性和继发性溶酶体。摄取β-VLDL后，酸性磷酸酶阳性细胞器的总体积在30分钟内增加了两倍，并且在另外三种形态不同的结构中发现了反应产物：管状溶酶体、膜堆叠以及池变宽的内质网。在β-VLDL孵育的10分钟、30分钟、1小时和4小时时，对五种酸性磷酸酶阳性细胞器各自占据细胞的比例进行了定量，并将它们的相对丰度与未接受脂蛋白刺激或孵育1小时白蛋白的对照进行了比较。继发性溶酶体区室体积在30分钟时达到峰值；然而，在随后的3.5小时内，反应逐渐转移到三个新的膜限定位置。我们的观察结果记录了脂蛋白摄取诱导的酸性磷酸酶阳性结构之间复杂的3D组织和空间关系。脂蛋白刺激的鸽单核细胞/巨噬细胞中酸性磷酸酶阳性溶酶体的3D组织模式在几个方面与先前在鸽动脉病变巨噬细胞中观察到的复杂溶酶体相似。
