Fluoro-edenite (FE), an asbestiform fiber, is responsible for many respiratory pathologies: chronic obstructive diseases, pleural plaques, fibrosis, and malignant mesothelioma. Macrophage migration inhibitory factor (MIF) is one of the first cytokines produced in response to lung tissue damage. Heme oxygenase-1 (HO-1) is a protein with protective effects against oxidative stress. It is up regulated by several stimuli including pro-inflammatory cytokines and factors that promote oxidative stress. In this research, the in vivo model of sheep lungs naturally exposed to FE was studied in order to shed light on the pathophysiological events sustaining exposure to fibers, by determining immunohistochemical lung expression of MIF and HO-1. Protein levels expression of HO-1 and MIF were also evaluated in human primary lung fibroblasts after exposure to FE fibers in vitro. In exposed sheep lungs, MIF and HO-1 immunoexpression were spread involving the intraparenchymal stroma around bronchioles, interstitium between alveoli, alveolar epithelium and macrophages. High MIF immunoexpression prevails in macrophages. Similar results were obtained in vitro, but significantly higher values were only detected for HO-1 at concentrations of 50 and 100 μg/mL of FE fibers. MIF and HO-1 expressions seem to play a role in lung self-protection against uncontrolled chronic inflammation, thus counteracting the strong link with cancer development, induced by exposure to FE. Further studies will be conducted in order to add more information about the role of MIF and HO-1 in the toxicity FE-induced.

中文翻译：

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暴露于石棉纤维的肺中的防御和保护机制：巨噬细胞迁移抑制因子和血红素加氧酶-1的作用。

氟石棉（FE）是一种石棉状纤维，可导致许多呼吸道疾病：慢性阻塞性疾病，胸膜斑块，纤维化和恶性间皮瘤。巨噬细胞迁移抑制因子（MIF）是响应肺组织损伤而产生的首批细胞因子之一。血红素加氧酶-1（HO-1）是一种具有抗氧化应激作用的蛋白质。它受到多种刺激的上调，包括促炎性细胞因子和促进氧化应激的因子。在这项研究中，研究了自然暴露于FE的绵羊肺的体内模型，以通过确定MIF和HO-1的免疫组织化学肺表达来揭示维持暴露于纤维的病理生理事件。在体外暴露于FE纤维后，还评估了人类原代肺成纤维细胞中HO-1和MIF的蛋白表达水平。在暴露的绵羊肺中，MIF和HO-1免疫表达在细支气管周围的实质内基质，肺泡之间的间质，肺泡上皮和巨噬细胞之间扩散。高MIF免疫表达普遍存在于巨噬细胞中。在体外获得了相似的结果，但仅在浓度为50和100μg/ mL的FE纤维中，HO-1的检测值明显更高。MIF和HO-1的表达似乎在针对不受控制的慢性炎症的肺自我保护中起作用，从而抵消了由于暴露于FE而导致的与癌症发展的紧密联系。为了添加更多关于MIF和HO-1在FE诱导的毒性中的作用的信息，将进行进一步的研究。