Protease Activity and the Role of the Endothelial Glycocalyx in Inflammation.

Protease Activity and the Role of the Endothelial Glycocalyx in Inflammation.
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DOI:
10.1016/j.ddmod.2011.05.004
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发表时间:
2011
期刊:
Drug discovery today. Disease models
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提出了一种控制炎症过程中白细胞-内皮 (WBC-EC) 粘附的新范例,其中内皮糖萼的脱落暴露了 EC 表面的粘附分子,从而促进了 WBC-EC 粘附。据推测,这种脱落的效应子是细胞外蛋白酶的激活,其中一种可能是锌依赖性内肽酶的基质金属蛋白酶(MMP)家族的成员。该糖萼作为 WBC-EC 粘附屏障的作用模型包括正常活性的细胞外蛋白水解酶(即脱落酶)的额外参与,其可能裂解蛋白聚糖或激活裂解糖萼中的 GAG 链的裂解酶。为了支持这一假设,进行了一些研究,这些研究已经证实了 EC 表面 MMP 酶原的同时激活、糖​​萼的脱落以及 WBC-EC 粘附的增强。
A new paradigm for governance of leukocyte-endothelium (WBC-EC) adhesion during the inflammatory process is presented in which shedding of the endothelial glycocalyx exposes adhesion molecules on the EC surface, which promotes WBC-EC adhesion. It is postulated that the effector of this shedding is the activation of extracellular proteases, one of which may be a member of the matrix metalloproteinase (MMP) family of zinc dependent endopetidases. This model for the role of the glycocalyx as a barrier to WBC-EC adhesion includes the additional participation of normally active extracellular proteolytic enzymes, i.e. sheddases, which may cleave proteoglycans or activate lyases that cleave GAG chains in the glycocalyx. In support of this hypothesis, studies are examined which have established the concurrent activation of MMP proenzymes on the EC surface, shedding of the glycocalyx, and enhanced WBC-EC adhesion.