Molecular and Biological Study on Roles of Colony-Stimulating Factors in the Formation of Granulomatous Lung Lesions.

肺结节病的特点是肺泡巨噬细胞大量聚集在肺的局部环境。为了探讨其作用机制，我们检测了几种集落刺激因子(CSF)的mRNA表达。我们从经支气管肺泡灌洗获得的炎性细胞中提取RNA，这些细胞主要由肺泡巨噬细胞和淋巴细胞组成。用合成的巨噬细胞集落刺激因子(M-CSF)、白细胞介素3(IL-3)和粒细胞巨噬细胞集落刺激因子(GM-CSF)的合成引物，用逆转录-聚合酶链式反应(RT-PCR)方法检测M-CSFmRNA在所有正常人、肺结节病和Farmer‘s肺病患者中的表达。IL-3mRNA均未检测到。20例肺结节病患者中有15例检测到GM-CSF mRNA，而正常人和Farmer‘s肺病患者均未检测到GM-CSF mRNA的表达。GM-CSF被认为对累积的…有贡献单核细胞的活化、分化和增殖使肺泡巨噬细胞产生更多的离子。值得注意的是，肺结节病和Farmer‘s肺病的GM-CSF mRNA表达结果存在差异，提示两种肉芽肿病的发病机制不同。我们还探讨了肺结节病GM-CSF mRNA表达与临床意义的关系。有mRNA表达的患者的支气管肺泡灌洗液淋巴细胞比例、CD4/8比值和血清ACE水平均显著高于无表达患者。从检测mRNA的时间进行的回顾性研究显示，mRNA的表达与胸片判断的临床病程不变或更差有关。前瞻性研究给出了类似的结果，从而证实了GM-CSF在肺结节病的发病机制中的重要作用。较少

Pulmonary sarcoidosis is characterized by the accumulation of a great number of alveolar macrophages at local milieu of the lung. In order to investigate its mechanism, We aimed to examine the expression of mRNA of several colony-stimulating factors (CSFs). We extracted RNA from inflammatory cells obtained by bronchoalveolar lavage, which were composed mainly of alveolar macrophages and lymphocytes. mRNA of interest was detected by reverse transcription-polymerase chain reaction (RT-PCR) method using synthesized primers of macrophage-CSF (M-CSF), interleukin-3 (IL-3), and granulocytemacrophage-CSF (GM-CSF).M-CSF mRNA was detected in all normal subjects, patients with pulmonary sarcoidosis, and patients with farmer's lung disease. Meanwhile, IL-3 mRNA was detected none of them. GM-CSF mRNA was detected in 15 of 20 patients with pulmonary sarcoidosis, whereas it was expressed in none of normal subjects and patients with farmer's lung disease. GM-CSF is assumed to contribute the accumulat … More ion of alveolar macrophages by activation, differentiation, and proliferation of monocytes. As it also has a fusing effect of alveolar macrophages, it may be involved in the formation of multinucleated giant cells within the granulomas.It is noteworthy that results of the expression of GM-CSF mRNA was contrasting between pulmonary sarcoidosis and farmer's lung disease, suggesting different pathogenetic mechanisms are working in these two granulomatous lung diseases.We also examined the relationship between the expression of GM-CSF mRNA and clinical significance in pulmonary sarcoidosis. Patients with mRNA expression had significantly higher proportion of bronchoalveolar lavage lymphocytes, CD4/8 ratio, and serum ACE levels than those without the expression. Retrospective study from the time when mRNA was examined revealed association between mRNA expression and unchanged or worse clinical course judged by chest X-ray films. Prospective study gave similar results, thus demonstrating substantial role of GM-CSF in the pathogenetic mechanism of pulmonary sarcoidosis. Less