Vascular endothelial cell proteoglycans are susceptible to cleavage by neutrophils.
Vascular endothelial cell proteoglycans are susceptible to cleavage by neutrophils.
复制标题
血管内皮细胞蛋白多糖易被中性粒细胞裂解。
DOI：
10.1161/01.atv.12.7.836
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Vercellotti,GM
中科院分区：
文献类型：
--
作者：
Key,NS;Platt,JL;Vercellotti,GM
硫酸乙酰肝素蛋白聚糖在体内与血管内皮细胞相关，在许多内皮功能中发挥重要作用，包括抑制血管内凝血和血浆蛋白和血细胞外渗。在这份报告中，我们证明，多形核中性粒细胞，以及无细胞的中性粒细胞上清液，导致快速和戏剧性的损失蛋白多糖从内皮细胞中的细胞溶解的证据的情况下。这种切割似乎对硫酸乙酰肝素具有相对的（尽管不是绝对的）选择性，并且由嗜酸性粒细胞衍生的丝氨酸蛋白酶介导。中性粒细胞弹性蛋白酶抑制剂似乎是最有效的蛋白多糖释放抑制剂。此外，纯化的人嗜中性粒细胞弹性蛋白酶也导致细胞蛋白聚糖的切割，尽管程度与嗜中性粒细胞或嗜中性粒细胞上清液不同。与所有其他含蛋白质的大分子相比，蛋白聚糖似乎特别容易受到嗜中性粒细胞介导的切割。本研究的结果可能与炎症过程中中性粒细胞与内皮细胞的相互作用密切相关，在此过程中，内皮硫酸乙酰肝素蛋白聚糖的丢失可能在经常伴随炎症的血管损伤中发挥关键作用。
Heparan sulfate proteoglycan associated with vascular endothelial cells in vivo plays an important role in a number of endothelial functions, including the inhibition of intravascular coagulation and extravasation of plasma proteins and blood cells. In this report, we demonstrate that polymorphonuclear neutrophils, as well as cell-free neutrophil supernatants, lead to a rapid and dramatic loss of proteoglycan from endothelial cells in the absence of evidence of cell lysis. This cleavage appears to be relatively (although not absolutely) selective for heparan sulfate and is mediated by neutrophil-derived serine proteases. Inhibitors of neutrophil elastase appear to be the most effective inhibitors of proteoglycan release. Furthermore, purified human neutrophil elastase also leads to cleavage of cellular proteoglycans, although not to the same extent as neutrophils or neutrophil supernatants. Proteoglycans compared with all other protein-containing macromolecules appear to be especially vulnerable to neutrophil-mediated cleavage. The results of this study may be germane to the interaction of neutrophils with endothelium during the inflammatory process, during which the loss of endothelial heparan sulfate proteoglycan may play a critical role in the vascular injury that often accompanies inflammation.