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Elevated bronchoalveolar concentrations of MCP-1 in patients with pulmonary alveolar proteinosis
K Iyonaga1, M Suga, T Yamamoto
1First Dept of Internal Medicine, Kumamoto University School of Medicine, Honjo, Japan.
Abstract:
Pulmonary alveolar proteinosis (PAP) is a rare disease of unknown aetiology characterized by accumulations of lipoproteinaceous material within the alveoli. The alveolar macrophages become increasingly foamy, and are thought to have a role in the pathogenesis of PAP. However, the mechanisms of macrophage recruitment are unclear. In the bronchoalveolar lavage fluid (BALF) of four patients with PAP and 20 normal control subjects, the following were examined: the monocyte chemotactic activity due to the chemokine monocyte chemoattractant protein (MCP)-1 with the use of a chemotactic chamber assay, the levels of MCP-1 by enzyme-linked immunosorbent assay, and the MCP-1 expression on lavage cells by immunocytochemistry and in situ hybridization. The monocyte chemotactic activity in the BALF of the PAP patients was markedly elevated, and the activity was completely absorbed by treatment with anti-MCP-1. The MCP-1 levels in the BALF were surprisingly high in the PAP group (25,100+/-472 pg x mL(-1)), whereas low levels of MCP-1 were detected in the normal control subjects (mean: never smokers 4.8; smokers 10.4 pg x mL(-1)). MCP-1 protein and messenger ribonucleic acid were expressed by macrophages from the PAP patients, and the expression was reduced according to foaming of the cells; there were monocyte-like macrophages with strong expression, small foamy cells with moderate expression, large foamy cells with a faint expression of MCP-1, and ghost cells with no expression. However, the increase of macrophage number in the PAP BALF was relatively small. These data suggest that monocyte chemoattractant protein(-1) expression by alveolar macrophages represents an amplification mechanism for the recruitment of additional macrophages to the alveoli in pulmonary alveolar proteinosis. It is possible that an ingestion of an excess of alveolar materials in pulmonary alveolar proteinosis may impair the macrophage function and the survival, resulting in the lack of a prominent increase in the macrophage number in bronchoalveolar lavage fluid.
Insights
Pulmonary alveolar proteinosis (PAP) involves alveolar macrophage dysfunction. Monocyte chemoattractant protein-1 (MCP-1) is highly expressed by PAP macrophages, potentially recruiting more cells to the lungs.
Area of Science:
- Pulmonary Medicine
- Immunology
- Cell Biology
Background:
- Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by lipoprotein accumulation in alveoli.
- Alveolar macrophages are implicated in PAP pathogenesis, but recruitment mechanisms are unclear.
Purpose of the Study:
- To investigate the role of monocyte chemoattractant protein-1 (MCP-1) in macrophage recruitment in PAP.
- To quantify MCP-1 levels and expression in bronchoalveolar lavage fluid (BALF) from PAP patients.
Main Methods:
- Analyzed BALF from PAP patients and controls for monocyte chemotactic activity using a chamber assay.
- Measured MCP-1 levels via enzyme-linked immunosorbent assay (ELISA).
- Assessed MCP-1 expression on lavage cells using immunocytochemistry and in situ hybridization.
Main Results:
- PAP patients exhibited markedly elevated monocyte chemotactic activity in BALF, fully neutralized by anti-MCP-1.
- MCP-1 levels were significantly higher in PAP patients (25,100 pg/mL) compared to controls (4.8-10.4 pg/mL).
- MCP-1 expression was detected in PAP macrophages, decreasing with cell foaming, despite a modest increase in overall macrophage numbers.
Conclusions:
- Alveolar macrophage MCP-1 expression may amplify macrophage recruitment in PAP.
- Impaired macrophage function or survival due to excessive material ingestion could explain the limited increase in macrophage count.