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Chemokine expression by small sputum macrophages in COPD
Marion Frankenberger1, Christiane Eder, Thomas P J Hofer
1Clinical Cooperation Group Inflammatory Lung Diseases, Asklepios Fachkliniken München-Gauting and Helmholtz Center Munich, Gauting, Germany. frankenberger@helmholtz-muenchen.de
Molecular Medicine (Cambridge, Mass.)
|February 18, 2011
Summary
In chronic obstructive pulmonary disease (COPD), small sputum macrophages significantly increase and express specific chemokines like CCL13, distinct from lipopolysaccharide-induced responses.
Area of Science:
- Pulmonary Medicine
- Immunology
- Cell Biology
Background:
- Small sputum macrophages are highly active and increase in inflammatory airway diseases like COPD.
- Elevated cytokines, chemokines, and proteases are observed in COPD sputum supernatants.
- These macrophages may contribute to airway inflammation and cell recruitment in COPD.
Purpose of the Study:
- To investigate chemokine expression profiles in sputum macrophages from COPD patients.
- To compare these profiles with cells from healthy donors and lipopolysaccharide (LPS)-induced inflammation models.
- To understand the specific role of small sputum macrophages in COPD pathogenesis.
Main Methods:
- Sputum induction for minimally invasive sample collection.
- Macrophage purification using RosetteSep technology.
- Flow cytometry and mRNA analysis for chemokine expression profiling.
Main Results:
- COPD patients exhibit a significantly higher proportion of small sputum macrophages (85.9%) compared to controls (12.9%).
- Small macrophages in COPD show markedly increased transcript and protein levels for CCL2, CCL7, CCL13, and CCL22, with CCL13 mRNA increasing over 100-fold.
- Active smokers without COPD also show increased small macrophages and chemokine expression.
- LPS inhalation in healthy volunteers increased small macrophages but induced a different chemokine pattern (upregulated CCL2/CCL7, downregulated CCL13).
Conclusions:
- Sputum macrophages in COPD display a unique CCL chemokine induction pattern.
- This pattern is distinct from the chemokine response observed after LPS-induced airway inflammation.
- Small sputum macrophages play a specific, disease-associated role in COPD, differing from general inflammatory responses.
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