Heparin is essential for the storage of specific granule proteases in mast cells
Heparin is essential for the storage of specific granule proteases in mast cells
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DOI：
10.1038/23481
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发表时间：
1999-08-19
期刊：
影响因子：
64.8
通讯作者：
Stevens, RL
中科院分区：
文献类型：
--
作者：
Humphries, DE;Wong, GW;Stevens, RL
所有哺乳动物都产生肝素，肝素是一种带负电荷的糖胺聚糖，是在腹膜腔和大多数结缔组织中发现的肥大细胞分泌颗粒的主要成分。虽然肝素是人体内研究最多的分子之一，但其生理功能尚未确定。在这里，我们描述了通过破坏N-脱乙酰基酶/N-磺基转移酶-2基因（1，2）产生的转基因小鼠，其不能表达完全硫酸化的肝素。骨骼肌中通常含有肝素的肥大细胞缺乏异染颗粒，并且不能储存可观数量的小鼠肥大细胞蛋白酶（mMCP）-4，mMCP-5和羧肽酶A（mMC-CPA），尽管它们含有大量的mMCP-7，我们还是从转基因小鼠的骨髓中培养了肥大细胞。尽管这些培养的细胞含有高水平的各种蛋白酶转录物，并且在其颗粒中具有大量的mMCP-6蛋白，但它们也未能表达mMCP-5和mMC-CPA。我们的数据表明，肝素通过翻译后机制控制肥大细胞内带正电荷的蛋白酶的特定盒的水平。
All mammals produce heparin, a negatively charged glycosaminoglycan that is a major constituent of the secretory granules of mast cells which are found in the peritoneal cavity and most connective tissues. Although heparin is one of the most studied molecules in the body, its physiological function has yet to be determined. Here we describe transgenic mice, generated by disrupting the N-deacetylase/N-sulphotransferase-2 gene(1,2), that cannot express fully sulphated heparin, The mast cells in the skeletal muscle that normally contain heparin lacked metachromatic granules and failed to store appreciable amounts of mouse mast-cell protease (mMCP)-4, mMCP-5 and carboxypeptidase A (mMC-CPA), even though they contained substantial amounts of mMCP-7, We developed mast cells from the bone marrow of the transgenic mice. Although these cultured cells contained high levels of various protease transcripts and had substantial amounts of mMCP-6 protein in their granules, they also failed to express mMCP-5 and mMC-CPA, Our data show that heparin controls, through a post-translational mechanism, the levels of specific cassettes of positively charged proteases inside mast cells.