硝苯地平和环孢素A相关的人类牙龈过度生长中的巨噬细胞和淋巴细胞亚群

Pernu H E, Knuuttila M L

Department of Periodontology and Geriatric Dentistry, Institute of Dentistry, University of Oulu, Finland.

J Periodontol. 2001 Feb;72(2):160-6. doi: 10.1902/jop.2001.72.2.160.

BACKGROUND

Nifedipine and cyclosporin A (CsA) induce gingival overgrowth. Both drugs have immunomodulating effects. It has been suggested that altered immune response is associated with drug-induced gingival overgrowth. In this study, we evaluated whether there were differences in macrophages and lymphocyte subpopulations in human nifedipine- and CsA-associated gingival overgrowth as compared with those in normal gingiva.

METHODS

Biopsy samples of overgrown gingiva were obtained from 9 nifedipine-treated cardiac outpatients, 13 CsA-treated renal transplant recipients including 9 patients who were also receiving nifedipine, and 30 healthy control individuals undergoing dental treatment. Serial 5 microm thick cryostat sections were stained with mAbs for CD20 (B-pan), CD68 (macrophages), CD4 (T-helper/inducer), and CD8 (T-cytotoxic/suppressor) using an avidin-biotin-horseradish peroxidase complex method. Numbers of mAb-labeled and all nucleated cells were determined in 3 areas: the connective tissue beneath the sulcular epithelium, the middle connective tissue, and the connective tissue beneath the oral epithelium. Distributions of each type of cell were expressed as percentages of mAb-labeled cells in relation to total number of nucleated cells in a counting zone. Significances of differences between groups were tested by means of the Kruskal-Wallis test, and between pairs of results by means of the Mann-Whitney U-test.

RESULTS

The proportion of CD8-labeled cells was significantly higher in connective tissue beneath the sulcular epithelium in the nifedipine group than in the controls (P = 0.014). In both medicated groups, the proportions of CD68-labeled cells were higher in all counting zones than in the controls, but statistically significantly only in the nifedipine group in the connective tissue beneath the oral epithelium (P = 0.008). No intergroup differences were found with respect to CD4- and CD20-labeled cells. The CD4/CD8 ratio was significantly lower in connective tissue beneath the sulcular epithelium in the nifedipine group than in the controls (P= 0.013).

CONCLUSION

The results support the idea that immune response may be altered in drug-induced gingival overgrowth.

背景

硝苯地平和环孢素A（CsA）可导致牙龈增生。这两种药物都具有免疫调节作用。有人提出免疫反应改变与药物性牙龈增生有关。在本研究中，我们评估了与正常牙龈相比，人类硝苯地平及CsA相关性牙龈增生中巨噬细胞和淋巴细胞亚群是否存在差异。

方法

从9名接受硝苯地平治疗的心脏门诊患者、13名接受CsA治疗的肾移植受者（其中9名同时也在服用硝苯地平）以及30名接受牙科治疗的健康对照个体获取增生牙龈的活检样本。使用抗生物素蛋白-生物素-辣根过氧化物酶复合物法，对连续的5微米厚冰冻切片用抗CD20（B细胞泛抗体）、CD68（巨噬细胞）、CD4（辅助性/诱导性T细胞）和CD8（细胞毒性/抑制性T细胞）单克隆抗体进行染色。在三个区域测定单克隆抗体标记细胞和所有有核细胞的数量：龈沟上皮下方的结缔组织、中间结缔组织以及口腔上皮下方的结缔组织。每种细胞类型的分布以计数区域中单克隆抗体标记细胞占所有有核细胞总数的百分比表示。组间差异的显著性通过Kruskal-Wallis检验进行检验，成对结果之间的差异通过Mann-Whitney U检验进行检验。

结果

硝苯地平组龈沟上皮下方结缔组织中CD8标记细胞的比例显著高于对照组（P = 0.014）。在两个用药组中，所有计数区域中CD68标记细胞的比例均高于对照组，但仅在口腔上皮下方结缔组织的硝苯地平组中有统计学显著性差异（P = 0.008）。在CD4和CD20标记细胞方面未发现组间差异。硝苯地平组龈沟上皮下方结缔组织中的CD4/CD8比值显著低于对照组（P = 0.013）。