Department of Bioengineering, The Pennsylvania State University, 205 Hallowell Bldg, University Park, PA 16802, USA.
Ann Biomed Eng. 2012 Apr;40(4):840-8. doi: 10.1007/s10439-011-0427-x. Epub 2011 Oct 8.
The endothelial cell (EC) surface is coated with a layer of polysaccharides linked to membrane-bound and trans-membrane proteoglycans that comprise the glycocalyx, which is augmented by adsorbed proteins derived from the blood stream. This surface layer has been shown to affect hemodynamics in small blood vessels of the microcirculation, the resistance to flow, and leukocyte (WBC) to EC adhesion. Parallel studies of WBC-EC adhesion in response to chemoattractants and cytokines, and shedding of constituents of the glycocalyx, have suggested a role for activation of extracellular proteases in mediating the dynamics of WBC adhesion in response to inflammatory and ischemic stimuli. Likely candidates among the many proteases present are the matrix metalloproteases (MMPs). Inhibition of MMP activation with sub-antimicrobial doses of doxycycline, or zinc chelators, has also inhibited WBC adhesion and shedding of glycans from the EC surface in response to the chemoattractant fMLP. Taken together, these studies suggest that shedding of the EC glycocalyx exposes adhesion receptors and thus enhances WBC-EC adhesion. Future therapeutic strategies for treating pathologies such as the low flow state and inflammation may benefit by further exploration of the mechanics of the glycocalyx in light of protease activation and shear-dependent effects.
内皮细胞 (EC) 表面覆盖着一层多糖，与膜结合和跨膜蛋白聚糖相连，构成糖萼，糖萼还被来自血流的吸附蛋白所增强。已经表明，这个表面层会影响微循环中小血管的血液动力学、流动阻力以及白细胞 (WBC) 与 EC 的黏附。对 WBC-EC 黏附对趋化因子和细胞因子的反应以及糖萼成分脱落的平行研究表明，细胞外蛋白酶的激活在介导白细胞黏附的动力学方面起着重要作用，以响应炎症和缺血性刺激。在众多存在的蛋白酶中，基质金属蛋白酶 (MMPs) 可能是候选酶。用亚抗菌剂量的强力霉素或锌螯合剂抑制 MMP 的激活，也抑制了白细胞对趋化因子 fMLP 的黏附和 EC 表面聚糖的脱落。综上所述，这些研究表明，EC 糖萼的脱落暴露出黏附受体，从而增强了 WBC-EC 的黏附。未来治疗低血流状态和炎症等病理的治疗策略可能会受益于进一步探索糖萼在蛋白酶激活和剪切依赖性影响下的机制。
