Cell Adhesion Molecule Expression in Human Periodatitis

由细菌感染引起的慢性炎症性疾病，包括成人牙周炎(AP)，其特征是活化的炎性细胞在局部聚集。我们检测了细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)和E-选择素(内皮细胞白细胞黏附分子-1；ELAM-1)是否参与了AP的损害。与正常健康献血者相比，AP患者的牙龈组织中这些分子的mRNA水平升高。免疫组织化学分析显示，牙周成纤维细胞也表达ICAM-1。因此，我们研究了ICAM-1在体外培养的人牙龈成纤维细胞(HGF)中的表达和调控。在转录控制下，细胞表面ICAM-1不仅被IL-1b、TNF-a或干扰素-g刺激，而且还被牙周病细菌(牙周病杆菌和中间普雷沃特氏菌)的声波提取物(SE)和来自大肠杆菌的内毒素所刺激。最后，HGF和Molt4细胞的结合分析表明，这些分子诱导了这些分子的功能，并且这种增加的结合被抗ICAM-1和白细胞功能相关分子-1(LFA-1)的mAb所阻断。因此，细胞因子和牙周病原菌诱导的牙周成纤维细胞上ICAM-1的过度表达可能与炎症牙周组织中携带LFA-1的白细胞的滞留和激活密切相关。

Chronic inflammatory diseases caused by bacterial infection, including adult periodontitis (AP), are characterized by a local accumulation of activated inflammatory cells. We examined whether intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin (endothelial leukocyte adhesion molecule-1 ; ELAM-1) are involved in AP lesions. Gingival tissues from AP patients showed increased levels of these molecules mRNA,compared with those form normal healthy donors. Immunohistological analysis revealed that ICAM-1 was also expressed by gingival fibroblasts. Therefore, we investigated the expression and regulation of ICAM-1 on cultured human gingival fibroblasts (HGF). Cell surface ICAM-1 was upregulated on HGF under transcriptional control by exposure not only to IL-1b, TNF-a, or IFN-g but also to sonic extracts (SE) from periodontopathic bacteria (Porphromonas gingivalis and Prevotella intermedia) and LPS from Escherichia coli. However, these stimuli induced only minimal expression of VCAM-1 and E-selectinon HGF.Finally, binding assays using HGF and Molt4 cells showed induced these molecules to be functional, and the increased binding was blocked by a combination of mAb against ICAM-1 and leukocyte function-associated molecule-1 (LFA-1). Thus, the overexpression of ICAM-1 on gingival fibroblasts induced by cytokines and periodontopathic bacteria is speculated to be deeply involved in the retention and activation of LFA-1 bearing leukocytes in inflamed gingiva.