Chemokine Expression by Small Sputum Macrophages in COPD

Marion Frankenberger

Christiane Eder

Thomas Hofer

Irene Heimbeck

Loems Ziegler-Heitbrock

Click here for additional data file.^{(220K, pdf)}

^{Clinical Cooperation Group “Inflammatory Lung Diseases,” Asklepios Fachkliniken München-Gauting and Helmholtz Center Munich, Gauting, Germany}

^{Comprehensive Pneumology Center (CPC), Ludwig-Maximilians University, Asklepios Fachkliniken München-Gauting and Helmholtz Center Munich, Munich, Germany}

^{EvA-Study Center Gauting, Helmholtz Center Munich, Gauting, Germany}

^{Institute of Lung Biology and Disease, Helmholtz Center Munich, Munich, Germany}

^{Asklepios Fachkliniken München-Gauting, Gauting, Germany}

Address correspondence and reprint requests to Marion Frankenberger, Helmholtz Center Munich, CPC Comprehensive Pneumology Center, Max-Lebsche-Platz 31, D-81377 Munich, Germany. Phone: +49-89-3187-1889; Fax: +49-89-3187-19-1889; E-mail: ed.nehcneum-ztlohmleh@regrebneknarf.

Received 2010 Oct 19; Accepted 2011 Feb 8.

Abstract

Small sputum macrophages represent highly active cells that increase in the airways of patients with inflammatory diseases such as chronic obstructive pulmonary disease (COPD). It has been reported often that levels of cytokines, chemokines and pro-teases are increased in sputum supernatants of these patients. In COPD, the small sputum macrophages may contribute to these supernatant proteins and recruit additional cells via specific chemokine expression patterns. We therefore investigated the expression profile of chemokines in sputum macrophages obtained from COPD patients in comparison to cells from healthy donors and cells isolated after inhalation of lipopolysaccharide (LPS). We used the minimally invasive procedure of sputum induction and have purified macrophages with the RosetteSep technology. Using macrophage purification and flow cytometry we show that in COPD small sputum macrophages account for 85.9% ± 8.3% compared with 12.9% ± 7.1% of total macrophages in control donors. When looking at chemokine expression we found, for the small macrophages in COPD, increased transcript and protein levels for CCL2, CCL7, CCL13 and CCL22 with a more than 100-fold increase for CCL13 mRNA (P < 0.001). Looking at active smokers without COPD, there is a substantial increase of small macrophages to 60% ± 15% and, here, chemokine expression is increased as well. In a model of airway inflammation healthy volunteers inhaled 20 μg of lipopolysaccharide (LPS), which resulted in an increase of small sputum macrophages from 18% ± 19% to 64% ± 25%. The pattern of chemokine expression was, however, different with an upregulation for CCL2 and CCL7, while CCL13 was downregulated three-fold in the LPS-induced small macrophages. These data demonstrate that sputum macrophages in COPD show induction of a specific set of CCL chemokines, which is distinct from what can be induced by LPS.

Abstract

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Footnotes

Online address: http://www.molmed.org

DISCLOSURES

The authors declare that they have no competing interests as defined by Molecular Medicine, or other interests that might be perceived to influence the results and discussion reported in this paper.

Footnotes

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