Prieditis H, Adamson I Y
Department of Pathology, University of Manitoba, Winnipeg, Canada.
J Leukoc Biol. 1996 Apr;59(4):534-8. doi: 10.1002/jlb.59.4.534.
Multinucleated giant cells (MGC) are a prominent feature of some chronic inflammatory states in the lung. These cells are formed by macrophage fusion, but how this process relates to the kinetics of alveolar macrophage (AM) production and proliferation is not clear. In this serial study, we compare AM kinetics and MGC formation after instilling carbon, silica, asbestos, bleomycin, and saline into the lungs of mice. Animals were killed up to 16 weeks later with [3H]thymidine injected 1 h before death. Counts of AM and MGC were carried out after bronchoalveolar lavage, and cell labeling was assessed by autoradiography. All test substances induced an inflammatory response with equal AM numbers recovered up to 2 weeks. Subsequently, the number returned to normal after carbon but remained elevated in the other groups. After carbon the lung structure was normal, there was no increase in AM label, and no MGC formed. Bleomycin-injected lungs progressed to fibrosis with only a brief, small increase in AM labeling and no MGC formation. After silica, and particularly asbestos, the lungs showed fibrosis, and many granulomas with large MGC were seen. Lavaged AM from these lungs showed a significant increase in DNA synthesis after 2 weeks, followed by higher numbers of MGC, none of which were labeled. Labeled AM tended to be free of particles, whereas MGC after 4 weeks contained many particles. The results indicate a relationship between AM proliferation and fusion, whereby AM growth appears to be prerequisite for cell infusion and MGC formation as a feature of granulomatous disease.
多核巨细胞（MGC）是肺部某些慢性炎症状态的一个显著特征。这些细胞由巨噬细胞融合形成，但这个过程与肺泡巨噬细胞（AM）产生和增殖的动力学之间的关系尚不清楚。在这项系列研究中，我们将碳、二氧化硅、石棉、博来霉素和生理盐水注入小鼠肺部后，比较了AM的动力学和MGC的形成。在处死动物前1小时注射[3H]胸腺嘧啶核苷，处死时间最长为16周后。支气管肺泡灌洗后进行AM和MGC计数，并通过放射自显影评估细胞标记情况。所有受试物质均引发炎症反应，在2周内回收的AM数量相等。随后，碳处理后AM数量恢复正常，而其他组的AM数量仍居高不下。碳处理后肺结构正常，AM标记无增加，也未形成MGC。注射博来霉素的肺发展为纤维化，AM标记仅有短暂、少量增加，且未形成MGC。二氧化硅处理后，尤其是石棉处理后，肺出现纤维化，可见许多含有大量MGC的肉芽肿。这些肺灌洗出的AM在2周后DNA合成显著增加，随后MGC数量增多，且均未标记。标记的AM往往不含颗粒，而4周后的MGC含有许多颗粒。结果表明AM增殖与融合之间存在关联，由此看来AM生长似乎是细胞聚集和MGC形成（作为肉芽肿性疾病的一个特征）的先决条件。
