Itoh A, Yamaguchi E, Furuya K, Kawakami Y
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Respirology. 1998 Dec;3(4):247-51. doi: 10.1111/j.1440-1843.1998.tb00130.x.
Several cytokines are involved in the pathophysiology of sarcoidosis. Granulocyte-macrophage colony-stimulating factor (GM-CSF) may be one of these cytokines because its mRNA is expressed by inflammatory cells obtained from the sarcoid lung. We thus asked two questions. Is GM-CSF secreted by bronchoalveolar lavage (BAL) cells? What type of cells express GM-CSF? GM-CSF secreted by the cultured BAL cells from 19 untreated sarcoid patients was measured by an enzyme-linked immunosorbent assay. The individual cells expressing GM-CSF mRNA were identified by in situ hybridization in seven patients. Spontaneous release of GM-CSF by BAL cells was demonstrated in one patient. When stimulated, BAL cells secreted GM-CSF in all subjects studied. In situ hybridization with digoxigenin-labelled GM-CSF cRNA probe revealed that the positive cells were round in shape and larger than lymphocytes, but smaller than large alveolar macrophages that are often irregular in shape. These results strongly indicated that small alveolar macrophages secrete GM-CSF in the sarcoid lesion. This phenomenon may contribute to the enhanced immunological activities observed in sarcoidosis.
几种细胞因子参与了结节病的病理生理学过程。粒细胞-巨噬细胞集落刺激因子(GM-CSF)可能是其中之一,因为从结节病肺组织获取的炎症细胞可表达其mRNA。因此,我们提出了两个问题。支气管肺泡灌洗(BAL)细胞会分泌GM-CSF吗?哪种类型的细胞表达GM-CSF?采用酶联免疫吸附测定法检测了19例未经治疗的结节病患者培养的BAL细胞分泌的GM-CSF。通过原位杂交在7例患者中鉴定出表达GM-CSF mRNA的单个细胞。在1例患者中证实了BAL细胞可自发释放GM-CSF。在所有研究对象中,当受到刺激时,BAL细胞均可分泌GM-CSF。用地高辛标记的GM-CSF cRNA探针进行原位杂交显示,阳性细胞呈圆形,比淋巴细胞大,但比通常形状不规则的大肺泡巨噬细胞小。这些结果有力地表明,小肺泡巨噬细胞在结节病病变中分泌GM-CSF。这种现象可能导致了结节病中观察到的免疫活性增强。