Espitia Pinzon Nathaly, Stroo Esther, 't Hart Bert A, Bol John G J M, Drukarch Benjamin, Bauer Jan, van Dam Anne-Marie
VU University Medical Center, Neuroscience Campus Amsterdam, Department of Anatomy and Neurosciences, Amsterdam, The Netherlands.
Biomedical Primate Research Center, Department of Immunobiology, Rijswijk, The Netherlands; University Groningen, University Medical Center, Department of Neuroscience, Groningen, The Netherlands.
PLoS One. 2014 Jun 24;9(6):e100574. doi: 10.1371/journal.pone.0100574. eCollection 2014.
Infiltration of leukocytes is a major pathological event in white matter lesion formation in the brain of multiple sclerosis (MS) patients. In grey matter lesions, less infiltration of these cells occur, but microglial activation is present. Thus far, the interaction of β-integrins with extracellular matrix proteins, e.g. fibronectin, is considered to be of importance for the influx of immune cells. Recent in vitro studies indicate a possible role for the enzyme tissue Transglutaminase (TG2) in mediating cell adhesion and migration. In the present study we questioned whether TG2 is present in white and grey matter lesions observed in the marmoset model for MS. To this end, immunohistochemical studies were performed. We observed that TG2, expressed by infiltrating monocytes in white matter lesions co-expressed β1-integrin and is located in close apposition to deposited fibronectin. These data suggest an important role for TG2 in the adhesion and migration of infiltrating monocytes during white matter lesion formation. Moreover, in grey matter lesions, TG2 is mainly present in microglial cells together with some β1-integrin, whereas fibronectin is absent in these lesions. These data imply an alternative role for microglial-derived TG2 in grey matter lesions, e.g. cell proliferation. Further research should clarify the functional role of TG2 in monocytes or microglial cells in MS lesion formation.
白细胞浸润是多发性硬化症（MS）患者脑白质病变形成过程中的主要病理事件。在灰质病变中，这些细胞的浸润较少，但存在小胶质细胞活化。迄今为止，β-整合素与细胞外基质蛋白（如纤连蛋白）的相互作用被认为对免疫细胞的流入很重要。最近的体外研究表明，组织转谷氨酰胺酶（TG2）在介导细胞黏附和迁移中可能发挥作用。在本研究中，我们质疑TG2是否存在于MS狨猴模型中观察到的白质和灰质病变中。为此，我们进行了免疫组织化学研究。我们观察到，TG2由白质病变中浸润的单核细胞表达，与β1-整合素共表达，且与沉积的纤连蛋白紧密相邻。这些数据表明TG2在白质病变形成过程中浸润单核细胞的黏附和迁移中起重要作用。此外，在灰质病变中，TG2主要存在于小胶质细胞中，同时伴有一些β1-整合素，而这些病变中不存在纤连蛋白。这些数据意味着小胶质细胞衍生的TG2在灰质病变中具有其他作用，如细胞增殖。进一步的研究应阐明TG2在MS病变形成中单核细胞或小胶质细胞中的功能作用。
