Floris Sarah, van den Born Jacob, van der Pol Susanne M A, Dijkstra Christine D, De Vries Helga E
Department of Molecular Cell Biology , Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
J Neuropathol Exp Neurol. 2003 Jul;62(7):780-90. doi: 10.1093/jnen/62.7.780.
Heparan sulfate proteoglycans (HSPGs) are known to participate in a wide range of biological events, including cellular trafficking. In this study we report that in situ cerebral blood vessels highly express HSPGs. Of the syndecan family, syndecan-2 is highly expressed on virtually all brain vessels and syndecan-1 and -3 are only present on larger blood vessels. These endothelial HSPGs have a functional role in monocyte diapedesis across brain endothelium, as assessed in our in vitro adhesion and migration assays. Our data indicate that heparin prevents monocyte adhesion to brain endothelium by interacting solely with the monocyte. Transendothelial migration of monocytes can be prevented by preincubation of brain endothelium with heparin by enzymatic removal of heparan sulphate side chains or by inhibition of cellular sulfation. Blocking of G-protein-dependent signaling in the monocytes prevented monocyte adhesion and migration to similar extent, suggesting that G-dependent signaling may be involved in HSPG-mediated monocyte adhesion and transendothelial migration. Our data demonstrate that brain endothelial HSPGs have a modulatory role in the transendothelial migration of monocytes in a direct and indirect fashion and may therefore contribute to the formation of neuroinflammatory lesions.
硫酸乙酰肝素蛋白聚糖（HSPGs）已知参与广泛的生物学事件，包括细胞运输。在本研究中，我们报告原位脑血管高度表达HSPGs。在Syndecan家族中，Syndecan-2在几乎所有脑血管上高度表达，而Syndecan-1和-3仅存在于较大的血管上。在我们的体外黏附和迁移试验中评估发现，这些内皮HSPGs在单核细胞穿过脑内皮的渗出过程中具有功能性作用。我们的数据表明，肝素仅通过与单核细胞相互作用来防止单核细胞黏附于脑内皮。通过用肝素预孵育脑内皮、酶促去除硫酸乙酰肝素侧链或抑制细胞硫酸化，可防止单核细胞的跨内皮迁移。阻断单核细胞中G蛋白依赖性信号传导在相似程度上阻止了单核细胞的黏附和迁移，这表明G依赖性信号传导可能参与HSPG介导的单核细胞黏附和跨内皮迁移。我们的数据表明，脑内皮HSPGs在单核细胞跨内皮迁移中具有直接和间接的调节作用，因此可能有助于神经炎性病变的形成。
