Kaser-Eichberger Alexandra, Schroedl Falk, Bieler Lara, Trost Andrea, Bogner Barbara, Runge Christian, Tempfer Herbert, Zaunmair Pia, Kreutzer Christina, Traweger Andreas, Reitsamer Herbert A, Couillard-Despres Sebastien
University Clinic of Ophthalmology and Optometry, Research Program for Experimental Ophthalmology and Glaucoma Research, Paracelsus Medical University Salzburg, Austria.
University Clinic of Ophthalmology and Optometry, Research Program for Experimental Ophthalmology and Glaucoma Research, Paracelsus Medical UniversitySalzburg, Austria; Institute of Anatomy, Paracelsus Medical UniversitySalzburg, Austria.
Front Cell Neurosci. 2016 Feb 9;10:23. doi: 10.3389/fncel.2016.00023. eCollection 2016.
Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with Iba1, the LYVE-1+ cell population likely represents a macrophage subpopulation, while a significant fraction of PROX1+ cells belong to the oligodendrocytic lineage based on their distribution and the expression of OLIG2. The response of these LYVE-1+ and PROX1+ cell subpopulations to pathological conditions, especially in spinal cord inflammatory conditions, needs to be further elucidated.
在生理条件下，尽管淋巴管广泛分布于身体其他部位，但人们认为中枢神经系统（CNS）中不存在淋巴管。最近在眼睛（另一个被认为无淋巴管的器官）的研究发现了许多表达淋巴管标志物的细胞。由于后者可能参与对病理状况的反应，我们通过免疫组织化学研究了脊髓中表达淋巴管标志物的细胞的存在情况。对年轻成年Fisher大鼠的脊髓进行检查，以观察淋巴管标志物PROX1和LYVE-1与细胞类型标志物Iba1、CD68、PGP9.5、OLIG2的共表达情况。大鼠皮肤用作淋巴管标志物的阳性对照。在整个脊髓白质和灰质的许多细胞核中检测到PROX1免疫反应性。这些细胞核与LYVE-1无关联。仅在脊髓表面的细胞以及与血管紧密相关的细胞中检测到LYVE-1的表达。发现这些细胞共表达Iba1，一种巨噬细胞和小胶质细胞标志物。此外，使用CD68（另一种在小胶质细胞和巨噬细胞中发现的标志物）进行的双重标记实验也显示在位于脊髓表面和与血管相邻的Iba1 +细胞中存在共定位。另一方面，在实质中发现的表达PROX1的细胞缺乏Iba1或PGP9.5，但这些细胞中有很大一部分显示出少突胶质细胞谱系标志物OLIG2的共表达。有趣的是，脊髓损伤后，表达LYVE-1的细胞聚集并重组为假定的血管前结构。正如预期的那样，用作阳性对照的大鼠皮肤显示出典型的淋巴管，其PROX1 +细胞核被LYVE-1免疫反应性包围。在成年大鼠脊髓中未检测到典型的淋巴管。然而，鉴定出了许多表达LYVE-1或PROX1的细胞。基于它们的定位以及与Iba1的重叠表达，LYVE-1 +细胞群可能代表巨噬细胞亚群，而很大一部分PROX1 +细胞基于其分布和OLIG2的表达属于少突胶质细胞谱系。这些LYVE-1 +和PROX1 +细胞亚群对病理状况的反应，尤其是在脊髓炎症状况下的反应，需要进一步阐明。
