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目的 探讨SARS冠状病毒 (SARS CoV)诱导的细胞凋亡在SARS发病机制中的意义。方法 采用原位末端标记(TUNEL)法与Cytokeratin(CK)及CD3、CD8、CD2 0、CD6 8单克隆抗体免疫组化双染色方法 ,对 6例SARS死亡患者的肺及肺外组织进行多种细胞凋亡状况的研究 ,并以免疫组化法检测凋亡相关蛋白Fas、Fas配体 (FasL)、Bcl 2和P5 3的表达。结果 与正常组织比较 ,SARS患者全身多器官组织细胞凋亡数目明显增多 ,尤以肺脏和免疫器官为甚 ,主要的凋亡细胞类型为CK阳性肺泡上皮细胞、终末支气管黏膜上皮细胞、CD3+ 细胞、CD8+ 细胞 ,以及少部分CD2 0 + 细胞和CD6 8+ 巨噬细胞。Fas蛋白主要于SARS肺组织内浸润的单个核细胞胞膜及胞质内表达 ,而FasL主要分布于SARS CoV感染的靶细胞 ,尤其是上述凋亡细胞内 ,肺及免疫器官内少数细胞亦表达FasL ,但Bcl 2及P5 3表达明显下调。结论 SARS CoV诱导的广泛且迅速的细胞凋亡可能为SARS患者肺脏及免疫器官的主要细胞损伤机制之一 ;SARS CoV诱导的主要凋亡细胞与体内SARS CoV主要的感染靶细胞相吻合 ;表达Fas的致敏T淋巴细胞与表达FasL的靶细胞结合介导的细胞凋亡可能为SARS CoV诱导细胞凋亡的重要机制之一 ,而Bcl 2和P5 3的表达下调可能参了细胞凋亡过程。
Objective To investigate the significance of apoptosis induced by SARS coronavirus (SARS CoV) in the pathogenesis of SARS. Methods TUNEL method and Cytokeratin (CK) and CD3, CD8, CD20, CD68 monoclonal antibody immunohistochemical double staining method were used to detect the lung and extrapulmonary tissues of 6 SARS patients Apoptosis and the expression of Fas, Fas ligand (FasL), Bcl 2 and P 5 3 were detected by immunohistochemistry. Results Compared with normal tissues, the number of apoptotic cells in multiple organ tissues of SARS patients was significantly increased, especially in lung and immune organs. The main apoptotic cells were CK positive alveolar epithelial cells, terminal bronchial epithelial cells, CD3 + cells , CD8 + cells, and a minority of CD20 + cells and CD6 8+ macrophages. Fas protein was mainly expressed in the membrane and cytoplasm of infiltrating mononuclear cells in lung tissues of SARS. FasL was mainly distributed in target cells infected by SARS CoV, especially in the above apoptotic cells. A few cells in lung and immune organs were also expressed FasL, but the expression of Bcl-2 and P53 was significantly down-regulated. Conclusion The extensive and rapid apoptosis induced by SARS CoV may be one of the major cell injury mechanisms in lung and immune organs of SARS patients. The major apoptotic cells induced by SARS CoV coincide with the major target cells infected by SARS CoV in vivo. The expression of Fas Of apoptosis induced by the combination of sensitized T lymphocytes and FasL-expressing target cells may be one of the important mechanisms of apoptosis induced by SARS CoV. The down-regulation of Bcl-2 and P53 may participate in the process of apoptosis.