Stabilin-1 and-2 constitute a novel family of fasciclin-like hyaluronan receptor homologues
Stabilin-1 and-2 constitute a novel family of fasciclin-like hyaluronan receptor homologues
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DOI：
10.1042/0264-6021:3620155
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发表时间：
2002-02-15
影响因子：
4.1
通讯作者：
Goerdt, S
中科院分区：
文献类型：
--
作者：
Politz, O;Gratchev, A;Goerdt, S
MS-1是一种由非连续性和血管生成性内皮细胞以及由交替激活的巨噬细胞（Mphi 2）表达的高分子量蛋白质，与肝窦内皮透明质酸清除受体在组织分布和生化特征方面相似。在本研究中，我们分别通过免疫层析和透明质酸亲和层析纯化这些蛋白质，胰蛋白酶肽测序并在小鼠和人中产生全长cDNA序列。新基因，即稳定蛋白-1和稳定蛋白-2，编码同源跨膜蛋白，其特征在于7个成束蛋白样粘附结构域、18-20个表皮生长因子结构域、1个X连接结构域和3 - 6个B-（X-7）-B透明质酸结合基序。Northern印迹实验揭示了在具有主要内皮窦的器官如肝、脾和淋巴结中存在两种稳定蛋白：在具有主要Mphi 2细胞的器官（如胎盘）和体外白细胞介素-4/糖皮质激素刺激的Mphi 2细胞中也检测到稳定蛋白-1 mRNA。针对人重组稳定蛋白-1制备的多克隆抗体证实了体内脾窦内皮细胞和体外Mphi 2中稳定蛋白-1蛋白的表达。基于蛋白质水平的高度相似性和独特的结构域组成，其不同于所有其他已知的成束蛋白样蛋白和透明质酸受体，稳定蛋白-1和稳定蛋白-2定义了一个新的成束蛋白样透明质酸受体同系物家族，其可能在血管功能和炎症过程中的细胞-细胞和细胞-基质相互作用中发挥作用。
MS-1, a high-molecular-mass protein expressed by non-continuous and angiogenic endothelial cells and by alternatively activated macrophages (Mphi2), and the hepatic sinusoidal endothelial hyaluronan clearance receptor are similar with respect to tissue distribution and biochemical characteristics. In the present study we purified these ' proteins by immuno- and hyaluronan-affinity chromatography respectively, sequenced tryptic peptides and generated full-length cDNA sequences in both mouse and human. The novel genes, i.e. stabilin-1 and stabilin-2, code for homologous transmembrane proteins featuring seven fasciclin-like adhesion domains, 18-20 epidermal-growth-factor domains, one X-link domain and three to six B-(X-7)-B hyaluronan-binding motifs, Northern-blotting experiments revealed the presence of both stabilins in organs with predominant endothelial sinuses such as liver, spleen and lymph node: stabilin-1 mRNA was also detected in organs with predominant Mphi2 cells, such as placenta, and in interleukin-4/glucocorticoid-stimulated Mphi2 cells in vitro. A polyclonal antibody made against human recombinant stabilin-1 confirmed the expression of stabilin-1 protein in splenic sinus endothelial cells in vivo and in Mphi2 in vitro. On the basis of high similarity at the protein level and the unique domain composition, which differs from that of all other known fasciclin-like proteins and hyaluronan receptors, stabilin-1 and stabilin-2 define a novel family of fasciclin-like hyaluronan receptor homologues that might play a role in cell-cell and cell-matrix interactions in vascular function and inflammatory processes.