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[Expression of GM-CSF in patients with pulmonary alveolar proteinosis]
1Department of Pulmonology, Second Affiliated Hospital of Medical School, Zhejiang University, Hangzhou 310009, China.
Objective:
To investigate the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) protein and mRNA in four patients with pulmonary alveolar proteinosis (PAP).
Methods:
GM-CSF levels were measured with a commercial ELISA kit. RT-PCR was employed to detect the expression of the GM-CSF mRNA in peripheral blood mononuclear cells (PBMC) and alveolar macrophages. To discover the possible mutations, the entire coding region of the GM-CSF cDNA was sequenced by the Sanger dideoxy-mediated chain termination method.
Results:
All patients, except for the one with secondary PAP showed no release of GM-CSF either from PBMC or from alveolar macrophages. The expression of the GM-CSF mRNA was normal in all patients, whereas a point mutation at position 382 of the GM-CSF cDNA from "T" to "C" was revealed by cDNA sequencing in one idiopathic PAP patient, which caused a change from isoleucine to threonine in amino acid 117 of the protein.
Conclusions:
Decreased GM-CSF production is associated with the pathogenesis of idiopathic PAP. A point mutation of the GM-CSF cDNA may partly contribute to the decreased GM-CSF production.
Insights
Decreased granulocyte-macrophage colony-stimulating factor (GM-CSF) production is linked to idiopathic pulmonary alveolar proteinosis (PAP). A specific GM-CSF gene mutation may contribute to this reduced protein production in PAP patients.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Genetics
Context:
- Pulmonary alveolar proteinosis (PAP) is a rare lung disorder characterized by surfactant accumulation.
- The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in PAP pathogenesis is not fully understood.
Purpose:
- To investigate the expression of GM-CSF protein and mRNA in patients with PAP.
- To identify potential genetic mutations in GM-CSF associated with PAP.
Summary:
- GM-CSF protein levels were significantly reduced in most PAP patients, with normal mRNA expression.
- A novel point mutation in the GM-CSF cDNA was identified in one idiopathic PAP patient, potentially affecting protein function.
- These findings suggest impaired GM-CSF production contributes to idiopathic PAP development.
Impact:
- Provides insights into the molecular mechanisms underlying idiopathic PAP.
- Highlights the potential role of GM-CSF deficiency in PAP pathogenesis.
- May inform future diagnostic or therapeutic strategies for PAP.