Apoptosis in the course of granulomatous inflammation in pulmonary sarcoidosis
Apoptosis in the course of granulomatous inflammation in pulmonary sarcoidosis
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DOI：
10.1034/j.1399-3003.1999.13f17.x
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发表时间：
1999-06-01
影响因子：
24.3
通讯作者：
Hara, N
中科院分区：
文献类型：
--
作者：
Kunitake, R;Kuwano, K;Hara, N
结节病是一种病因不明的慢性炎症性疾病，其特征是形成非坏死性肉芽肿。病程通常是自限性的，肉芽肿会自发消退。在免疫系统中，Fas抗原（Fas）和Fas配体（FasL）通过诱导细胞凋亡参与免疫反应的下调。因此，有人推测Fas/ Fast途径和细胞凋亡可能与结节病肉芽肿性炎症的过程中，末端脱氧核苷酸转移酶介导的生物素缺口末端标记（TUNEL）进行评估脱氧核糖核酸链断裂作为一个特征的细胞凋亡。免疫组化检测Fas和Fast蛋白，逆转录聚合酶链反应（RT-PCR）和RT原位PCR检测Fast信使核糖核酸（mRNA），TUNEL法在结节病患者的上皮样组织细胞和淋巴细胞、肉芽肿内和支气管肺泡灌洗液（BAL）淋巴细胞中检测到阳性信号。在这些细胞中也检测到Fas阳性信号。20例结节病患者中有15例BAL淋巴细胞表达FastmRNA，而10例正常肺组织中只有1例表达FastmRNA。Fast蛋白在肉芽肿周围和肉芽肿内的淋巴细胞中表达。TUNEL结果与结节病患者的临床病程密切相关，上皮样组织细胞和炎性细胞的凋亡可能参与了肉芽肿性炎症的过程。Fas、Fast等细胞凋亡调控因子在肺结节病肉芽肿性炎症中的作用有待进一步研究。
Sarcoidosis is a chronic inflammatory disease of unknown aetiology characterized by the formation of non-necrotizing granulomas. The course of disease is usually self-limiting with the spontaneous resolution of granuloma. In the immune system, Fas antigen (Fas) acid Fas ligand (FasL) are involved in the down regulation of immune reactions by inducing apoptosis. Therefore, it was hypothesized that the Fas/ Fast pathway and apoptosis may be associated with the course of granulomatous inflammation in sarcoidosis.Terminal deoxynucleotidyl transferase-mediated biotin nick end-labelling (TUNEL) was performed to assess deoxyribonucleic acid strand breakages as a characteristic of apoptosis. Immunohistochemistry was also performed to detect Fas and Fast protein, and reverse transcriptase polymerase chain reaction (RT-PCR) and RT in situ PCR to detect Fast messenger ribonucleic acid (mRNA).Positive signals for TUNEL were detected in epithelioid histiocytes and lymphocytes,within granulomas and in bronchoalveolar lavage (BAL) lymphocytes from patients with sarcoidosis. Positive signals for Fas were also detected in these cells. Fast mRNA was expressed in BAL lymphocytes from 15 of 20 patients with sarcoidosis, but from only one of 10 patients with normal Lung parenchyma. Fast protein was expressed in lymphocytes surrounding and within the granuloma. There was a significant correlation between the result of TUNEL and clinical course in patients with sarcoidosis.Apoptosis in epithelioid histiocytes and inflammatory cells seems to participate in the course of granulomatous inflammation. Further studies are needed to determine the role of Fas, Fast and other regulatory factors in apoptosis in the granulomatous inflammation in pulmonary sarcoidosis.