Antoniades H N, Neville-Golden J, Galanopoulos T, Kradin R L, Valente A J, Graves D T
Center for Blood Research, Harvard School of Public Health, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5371-5. doi: 10.1073/pnas.89.12.5371.
Macrophages are thought to play an important role in the pathologic changes associated with idiopathic pulmonary fibrosis (IPF). The mechanisms for increased monocyte/macrophage recruitment in IPF are unknown. Monocyte chemoattractant protein 1 (MCP-1) is the predominant monocyte chemoattractant secreted by a variety of different cell types in culture. We examined the expression of MCP-1 mRNA and its protein product in vivo in IPF and non-IPF lung specimens by in situ hybridization and immunocytochemistry. The cell types expressing MCP-1 in vivo were identified by immunostaining with specific antibodies. We demonstrated the expression of MCP-1 mRNA in pulmonary epithelial cells, in monocytes/macrophages, and in vascular endothelial and smooth muscle cells. Lung epithelial cells in patients with IPF strongly expressed MCP-1 mRNA and its protein product. In contrast, epithelial cells in non-IPF specimens did not express MCP-1 mRNA. Macrophages and vascular endothelial and smooth muscle cells were shown to express MCP-1 in both IPF and non-IPF lung specimens. These findings provide a basis for the understanding of the in vivo physiologic processes that mediate monocyte/macrophage recruitment and infiltration in the lung interstitium and the pathologic state contributing to an increased alveolar monocyte/macrophage population and inflammation in IPF.
巨噬细胞被认为在与特发性肺纤维化(IPF)相关的病理变化中起重要作用。IPF中单核细胞/巨噬细胞募集增加的机制尚不清楚。单核细胞趋化蛋白1(MCP-1)是培养的多种不同细胞类型分泌的主要单核细胞趋化剂。我们通过原位杂交和免疫细胞化学检测了IPF和非IPF肺标本中MCP-1 mRNA及其蛋白产物的体内表达。通过用特异性抗体进行免疫染色来鉴定体内表达MCP-1的细胞类型。我们证明了MCP-1 mRNA在肺上皮细胞、单核细胞/巨噬细胞以及血管内皮和平滑肌细胞中的表达。IPF患者的肺上皮细胞强烈表达MCP-1 mRNA及其蛋白产物。相比之下,非IPF标本中的上皮细胞不表达MCP-1 mRNA。在IPF和非IPF肺标本中,巨噬细胞以及血管内皮和平滑肌细胞均显示表达MCP-1。这些发现为理解介导单核细胞/巨噬细胞在肺间质中募集和浸润的体内生理过程以及导致IPF中肺泡单核细胞/巨噬细胞数量增加和炎症的病理状态提供了基础。