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Expression of monocyte chemoattractant protein 1 mRNA in human idiopathic pulmonary fibrosis
H N Antoniades1, J Neville-Golden, T Galanopoulos
1Center for Blood Research, Harvard School of Public Health, Boston, MA 02115.
Abstract:
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.
Insights
Idiopathic pulmonary fibrosis (IPF) involves increased lung inflammation. Monocyte chemoattractant protein 1 (MCP-1) is highly expressed by lung epithelial cells in IPF, driving monocyte recruitment.
Area of Science:
- Pulmonary Medicine
- Immunology
- Cell Biology
Background:
- Macrophages are implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis.
- Mechanisms of increased monocyte/macrophage recruitment in IPF remain unclear.
- Monocyte chemoattractant protein 1 (MCP-1) is a key chemoattractant for monocytes.
Purpose of the Study:
- To investigate the in vivo expression and cellular sources of MCP-1 in IPF lung specimens.
- To elucidate the role of MCP-1 in mediating monocyte/macrophage infiltration in IPF.
Main Methods:
- In situ hybridization to detect MCP-1 mRNA.
- Immunocytochemistry to identify MCP-1 protein expression.
- Immunostaining to identify cell types expressing MCP-1 in IPF and non-IPF lungs.
Main Results:
- MCP-1 mRNA and protein were expressed by pulmonary epithelial cells, monocytes/macrophages, and vascular cells in IPF lungs.
- Epithelial cells in IPF lungs showed strong MCP-1 expression, unlike in non-IPF lungs.
- Macrophages and vascular cells expressed MCP-1 in both IPF and non-IPF specimens.
Conclusions:
- Lung epithelial cells are a significant source of MCP-1 in IPF.
- These findings clarify in vivo mechanisms of monocyte/macrophage recruitment in IPF.
- Elevated MCP-1 contributes to the inflammatory infiltrate in IPF.