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作 者:周同[1] 张玉梅[1] 李晓[1] 吴开胤[1] 邹杰[1] 顾巧丽[2] 张雁云[2] 张冬青[2] 陈楠[1]
机构地区:[1]上海交通大学医学院瑞金医院肾内科 [2]上海交通大学医学院上海市免疫学研究所,上海200025
出 处:《细胞生物学杂志》2006年第5期752-756,共5页Chinese Journal of Cell Biology
基 金:国家自然科学基金(No.39970340;No.30570865);上海市科委基金(No.02ZB14041;No.034119916)资助项目~~
摘 要:DC-SIGN(DC-specificICAM-grabbingnon-integrin,亦称CD209)属树突状细胞(DC)表面C型凝集素的膜蛋白。作为DC黏附及模式识别受体,其参与介导了DC的炎症组织迁移,识别捕获病原微生物,以及随后激活静息T细胞启动的免疫应答。为此观察了DC-SIGN及DC-SIGN+DC在肾炎患者肾组织中表达和分布,以及DC-SIGN在炎性状态下培养人肾小管上皮细胞表达,探讨与肾小管间质炎症病变和损伤的关系。结果显示,DC-SIGN在正常肾组织基本不表达,而在肾炎早期即以肾小管上皮细胞为主表达上调,且随肾小管间质病变程度加重表达增强(P<0.01),与肾小管间质病变程度明显相关(P<0.01)。此外,DC-SIGN在经TNF-α刺激炎性状态下的人肾小管上皮细胞也明显表达。进一步发现,DC-SIGN+DC在肾炎早期以肾间质为主分布聚集,也随肾小管间质病变程度加重明显增多(P<0.01),与肾小管间质病变程度显著相关(P<0.01),也与DC-SIGN表达相关联(P<0.01)。另外,DC-SIGN+DC在肾小管间质分布数量与肾炎患者肾功能改变明显相关(P<0.05)。研究结果提示,DC-SIGN也是肾小管间质早期炎症的启动参与因素,其介导DC可能也参与了人肾炎肾小管间质的免疫损伤机制。DC-specific ICAM-grabbing non-integrin (DC-SIGN, CD209), the pattern recognition receptor and adhesion receptor of dendritic cell (DC), belongs to C-type lectin and plays an important role in DC migration and adhesion, inflammatory response, activating naive T cells, initiating immune response and immune escape of pathogens and tumors. In this study, we observed the expression and distribution of DC-SIGN and DC-SIGN^+ DC in renal tissue with nephropathy, and the presence of DC-SIGN on cultured human renal tubular epithelial cells under inflammatory condition. The expression of DC-SIGN was up-regulated in tubular epithelial cells from the early stage of nephritis on, which extent was increased consistent with the progression of nephropathy (P〈0.01) and correlated tightly with the degree of tubular interstitial fibrosis (P〈0.01). In vitro, the expression of DC-SIGN on cultured human renal tubular epithelial cells was elevated in the presence of TNF-α. In addition, DC-SIGN^+ DC was distributed mainly among renal interstitial area, which increased significantly with the progression of nephropathy (P〈0.01) and correlated with degree of renal tubularinterstitial fibrosis (P〈0.01) and the extent of DC-SIGN (P〈0.01). The number of DC-SIGN^+ DC was associated markedly with renal function (P〈0.05). DC-SIGN may mediate DC on the renal tubular interstitial injury induced by an immuno-inflammatory response.
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