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

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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