Moll Roland, Sievers Evelyn, Hämmerling Bettina, Schmidt Ansgar, Barth Mareike, Kuhn Caecilia, Grund Christine, Hofmann Ilse, Franke Werner W
Institute of Pathology, Philipps University of Marburg, 35033 Marburg, Germany.
Cell Tissue Res. 2009 Jan;335(1):109-41. doi: 10.1007/s00441-008-0700-y. Epub 2008 Nov 18.
The lymph node sinus are channel structures of unquestionable importance in immunology and pathology, specifically in the filtering of the lymph, the transport and processing of antigens, the adhesion and migration of immune cells, and the spread of metastatic cancer cells. Our knowledge of the cell and molecular biology of the sinus-forming cells is still limited, and the origin and biological nature of these cells have long been a matter of debate. Here, we review the relevant literature and present our own experimental results, in particular concerning molecular markers of intercellular junctions and cell differentiation. We show that both the monolayer cells lining the sinus walls and the intraluminal virgultar cell meshwork are indeed different morphotypes of the same basic endothelial cell character, as demonstrated by the presence of a distinct spectrum of general and lymphatic endothelial markers, and we therefore refer to these cells as sinus endothelial/virgultar cells (SEVCs). These cells are connected by unique adhering junctions, termed complexus adhaerentes, characterized by the transmembrane glycoprotein VE-cadherin, combined with the desmosomal plaque protein desmoplakin, several adherens junction plaque proteins including alpha- and beta-catenin and p120 catenin, and components of the tight junction ensemble, specifically claudin-5 and JAM-A, and the plaque protein ZO-1. We show that complexus adhaerentes are involved in the tight three-dimensional integration of the virgultar network of SEVC processes along extracellular guidance structures composed of paracrystalline collagen bundle "stays". Overall, the SEVC system might be considered as a local and specific modification of the general lymphatic vasculature system. Finally, physiological and pathological alterations of the SEVC system will be presented, and the possible value of the molecular markers described in histological diagnoses of autochthonous lymph node tumors will be discussed.
淋巴结窦是免疫学和病理学中具有毋庸置疑重要性的通道结构，特别是在淋巴过滤、抗原运输与处理、免疫细胞黏附和迁移以及转移性癌细胞扩散方面。我们对形成窦的细胞的细胞和分子生物学的了解仍然有限，这些细胞的起源和生物学特性长期以来一直是一个有争议的问题。在这里，我们回顾相关文献并展示我们自己的实验结果，特别是关于细胞间连接和细胞分化的分子标记。我们表明，窦壁内衬的单层细胞和腔内的网状细胞网络确实是具有相同基本内皮细胞特征的不同形态类型，这通过存在一系列独特的一般和淋巴管内皮标记得以证明，因此我们将这些细胞称为窦内皮/网状细胞（SEVCs）。这些细胞通过独特的黏附连接相连，称为复合黏附连接，其特征是跨膜糖蛋白VE-钙黏蛋白，与桥粒斑蛋白桥粒芯蛋白、几种黏附连接斑蛋白（包括α-连环蛋白、β-连环蛋白和p120连环蛋白）以及紧密连接复合体的成分（特别是闭合蛋白-5和JAM-A）和斑蛋白ZO-1结合。我们表明，复合黏附连接参与了SEVCs过程的网状网络沿着由平行排列的胶原束“支柱”组成的细胞外引导结构的紧密三维整合。总体而言，SEVC系统可被视为一般淋巴管系统的局部和特异性修饰。最后，将介绍SEVC系统的生理和病理改变，并讨论所描述的分子标记在原发性淋巴结肿瘤组织学诊断中的可能价值。
