Politz Oliver, Gratchev Alexei, McCourt Peter A G, Schledzewski Kai, Guillot Pierre, Johansson Sophie, Svineng Gunbjorg, Franke Peter, Kannicht Christoph, Kzhyshkowska Julia, Longati Paola, Velten Florian W, Johansson Staffan, Goerdt Sergij
Department of Dermatology, University Medical Center Mannheim, Ruprecht Karls University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68135 Mannheim, Germany.
Biochem J. 2002 Feb 15;362(Pt 1):155-64. doi: 10.1042/0264-6021:3620155.
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.
MS-1是一种由非连续性和血管生成性内皮细胞以及替代性活化巨噬细胞（Mphi2）表达的高分子量蛋白质，肝窦内皮透明质酸清除受体在组织分布和生化特性方面与之相似。在本研究中，我们分别通过免疫亲和色谱和透明质酸亲和色谱纯化了这些蛋白质，对胰蛋白酶肽段进行了测序，并在小鼠和人类中生成了全长cDNA序列。这些新基因，即稳定素-1和稳定素-2，编码同源跨膜蛋白，其具有七个类成束蛋白样黏附结构域、18 - 20个表皮生长因子结构域、一个X-连锁结构域以及三到六个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脏、脾脏和淋巴结中均存在这两种稳定素：在具有主要Mphi2细胞的器官如胎盘中，以及在体外白细胞介素-4/糖皮质激素刺激的Mphi2细胞中也检测到了稳定素-1 mRNA。一种针对人重组稳定素-1制备的多克隆抗体证实了稳定素-1蛋白在体内脾窦内皮细胞和体外Mphi2中的表达。基于蛋白质水平的高度相似性以及与所有其他已知类成束蛋白样蛋白和透明质酸受体不同的独特结构域组成，稳定素-1和稳定素-2定义了一个新的类成束蛋白样透明质酸受体同源物家族，它们可能在血管功能和炎症过程中的细胞间及细胞与基质相互作用中发挥作用。
