Proteolytic enzymes of mast cell granules degrade low density lipoproteins and promote their granule-mediated uptake by macrophages in vitro.
Proteolytic enzymes of mast cell granules degrade low density lipoproteins and promote their granule-mediated uptake by macrophages in vitro.
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DOI：
10.1016/s0021-9258(18)81685-4
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发表时间：
1989-06
期刊：
影响因子：
--
通讯作者：
J. Kokkonen;P. Kovanen
中科院分区：
文献类型：
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作者：
J. Kokkonen;P. Kovanen
从大鼠血清肥大细胞胞吐的分泌颗粒结合低密度脂蛋白（LDL），并且在被巨噬细胞吞噬时，将结合的LDL携带到这些细胞中（Kokkonen，J.O.，和Kovanen，P. T.等人（1987）Proc. Acad. Sci.联合S. A. 84，2287-2291）。LDL与颗粒的结合通过LDL的载脂蛋白B（apo B）组分与颗粒的肝素蛋白聚糖组分之间的相互作用介导。在这里，我们报告如何降解载脂蛋白B的中性蛋白酶的颗粒影响颗粒介导的摄取LDL培养的小鼠巨噬细胞。在孵育过程中的LDL与蛋白水解活性颗粒，LDL的吸收率增加了10倍，而在孵育过程中与蛋白水解活性颗粒，它增加了50倍，在蛋白水解过程中的吸收率的增加与apoB降解的程度。蛋白水解活性颗粒增强LDL摄取的5倍能力是由于它们结合LDL的能力更强，因此将其携带到巨噬细胞中。结合到蛋白水解活性颗粒的LDL的电子显微镜分析揭示了融合LDL的大球形颗粒。颗粒结合的颗粒的直径范围高达90 nm，相比之下，天然LDL和LDL结合蛋白水解活性颗粒的平均直径为22 nm。结果表明，颗粒蛋白酶通过诱导颗粒结合的LDL的融合，增加了每单位重量颗粒肝素蛋白聚糖结合的LDL的量。因此，肥大细胞颗粒的两种组分，蛋白酶和肝素蛋白聚糖，在体外协同作用以促进巨噬细胞对LDL的摄取。
Secretory granules exocytosed from rat serosal mast cells bind low density lipoprotein (LDL), and on being phagocytosed by macrophages, carry the bound LDL into these cells (Kokkonen, J. O., and Kovanen, P. T. (1987)Proc. Natl. Acad. Sci. U. S. A. 84, 2287–2291). The binding of LDL to the granules is mediated through interactions between the apolipoprotein B (apoB) component of LDL and the heparin proteoglycan component of the granules. Here we report how degradation of apoB by the neutral proteases of the granules affects the granule-mediated uptake of LDL by cultured mouse macrophages. During incubation of LDL with proteolytically inactive granules, the rate of uptake of LDL by macrophages increased by 10-fold; whereas during incubation with proteolytically active granules, it increased by 50-fold, the increase in the rate of uptake during proteolysis correlating with the degree of apoB degradation. The 5-fold greater capacity of the proteolytically active granules to enhance the uptake of LDL resulted from their greater capacity to bind LDL, and consequently, to carry it into the macrophages. Electron microscopic analysis of LDL bound to the proteolytically active granules disclosed large spherical particles of fused LDL. The diameters of the granulebound particles ranged up to 90 nm compared with an average diameter of 22 nm for both native LDL and the LDL bound to proteolytically inactive granules. The results show that granule proteases, by inducing fusion of granule-bound LDL, increase the amount of LDL bound per unit weight of granule heparin proteoglycan. Hence, the two components of mast cell granules, the proteases and the heparin proteoglycan, act in concert to promote the uptake of LDL by macrophagesin vitro.