Takahashi M, Mimura Y, Hayashi Y
Department of Ophthalmology, School of Medicine, University of Tokushima, Japan.
Pathobiology. 1996;64(5):269-74. doi: 10.1159/000164058.
We have analyzed the role of cell adhesion molecules during the development of autoimmune dacryodenitis in an NFS/sld mouse model for primary Sjögren's syndrome. The expression of cell adhesion molecules was assessed by RT-PCR and immunohistochemistry. We detected an up-regulation of local cell adhesion molecule genes (ICAM-1, LFA-1, CD44 and Mel-14) in the course of autoimmune lacrimal gland diseases. Immunohistochemically, ICAM-1 was localized exclusively in the endothelial cells of variously sized blood vessels before the onset of disease, and LFA-1, CD44 and Mel-14, expressing infiltrating cells, were found within these lesions. When the therapeutic effects of blocking cell adhesion molecules in vivo were examined, antibodies to ICAM-1 in combination with anti-LFA-1 prevented the development of autoimmune lacrimal gland diseases in NFS/sld mice. These data suggest that in Sjögren's syndrome-like autoimmune dacryoadenitis in NFS/sld mutant mice, the ICAM-1/LFA-1 pathway may play a crucial role in the development and subsequent progression of T-cell-mediated autoimmunity in the lacrimal glands.
我们在原发性干燥综合征的NFS/sld小鼠模型中，分析了细胞黏附分子在自身免疫性泪腺炎发展过程中的作用。通过逆转录聚合酶链反应（RT-PCR）和免疫组织化学评估细胞黏附分子的表达。我们检测到在自身免疫性泪腺疾病过程中，局部细胞黏附分子基因（细胞间黏附分子-1（ICAM-1）、淋巴细胞功能相关抗原-1（LFA-1）、CD44和Mel-14）上调。免疫组织化学显示，在疾病发作前，ICAM-1仅定位于大小各异的血管内皮细胞中，而在这些病变中发现了表达LFA-1、CD44和Mel-14的浸润细胞。当检测体内阻断细胞黏附分子的治疗效果时，抗ICAM-1抗体与抗LFA-1抗体联合使用可预防NFS/sld小鼠自身免疫性泪腺疾病的发展。这些数据表明，在NFS/sld突变小鼠的类干燥综合征自身免疫性泪腺炎中，ICAM-1/LFA-1通路可能在泪腺中T细胞介导的自身免疫的发展及后续进展中起关键作用。
