Mouse LYVE-1 is an endocytic receptor for hyaluronan in lymphatic endothelium
Mouse LYVE-1 is an endocytic receptor for hyaluronan in lymphatic endothelium
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DOI：
10.1074/jbc.m011004200
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发表时间：
2001-06-01
影响因子：
4.8
通讯作者：
Jackson, DG
中科院分区：
文献类型：
--
作者：
Prevo, R;Banerji, S;Jackson, DG
糖胺聚糖透明质酸是炎症、伤口愈合和瘤形成期间组织中细胞迁移的关键底物。与其他基质成分不同，透明质酸（HA）转化迅速，但大多数降解不是发生在局部，而是发生在远处淋巴结内，其机制尚不清楚。虽然尚不清楚哪些受体参与透明质酸在血管内的结合和摄取，但一个可能的候选者是我们实验室最近描述的淋巴内皮透明质酸受体LYVE-1（Banerji，S.，倪，J.，王，S.，Clasper，S.，苏，J.，塔米河，琼斯，M.，和杰克逊，D.G.（1999）J. Cell Biol.144，789-891）。在这里，我们提出的证据表明，LYVE-1参与了透明质酸的吸收淋巴管内皮细胞使用一个新的小鼠LYVE-1的直系同源物确定EST数据库。我们表明，小鼠LYVE-1结合和内化透明质酸在体外转染的293 T成纤维细胞，并证明使用免疫电镜，它是均匀分布在管腔和近腔表面的淋巴管在体内。此外，我们通过特异性抗血清表明，小鼠LYVE-1的表达仍然局限于缺乏CD 44功能基因的纯合敲除小鼠中的表达，CD 44是LYVE-1的最接近的同源物，也是迄今为止已知的唯一其他Link超家族HA受体。总之，这些结果表明LYVE-1在HA从组织转运到淋巴中的作用，并暗示必须存在可以补偿CD 44功能丧失的其他新型透明质酸受体。
glycosaminoglycan hyaluronan is a key substrate for cell migration in tissues during inflammation, wound healing, and neoplasia. Unlike other matrix components, hyaluronan (HA) is turned over rapidly, yet most degradation occurs not locally but within distant lymph nodes, through mechanisms that are not yet understood. While it is not clear which receptors are involved in binding and uptake of hyaluronan within the lymphatics, one likely candidate is the lymphatic endothelial hyaluronan receptor LYVE-1 recently described in our laboratory (Banerji, S., Ni, J., Wang, S., Clasper, S., Su, J., Tammi, R., Jones, M., and Jackson, D.G. (1999) J. Cell Biol. 144, 789-891.). Here we present evidence that LYVE-1 is involved in the uptake of hyaluronan by lymphatic endothelial cells using a new murine LYVE-1 orthologue identified from the EST data base. We show that mouse LYVE-1 both binds and internalizes hyaluronan in transfected 293T fibroblasts in vitro and demonstrate using immunoelectron microscopy that it is distributed equally among the luminal and abluminal surfaces of lymphatic vessels in vivo. In addition, we show by means of specific antisera that expression of mouse LYVE-1 remains restricted to the lymphatics in homozygous knockout mice lacking a functional gene for CD44, the closest homologue of LYVE-1 and the only other Link superfamily HA receptor known to date. Together these results suggest a role for LYVE-1 in the transport of HA from tissue to lymph and imply that further novel hyaluronan receptors must exist that can compensate for the loss of CD44 function.