Abstract
BackgroundCOPD patients have increased numbers of macrophages and neutrophils in the lungs. Interleukin-6 (IL-6) trans-signaling via its soluble receptor sIL-6R, governs the influx of innate immune cells to inflammatory foci through regulation of the chemokine CCL3. We hypothesized that there would be enhanced levels of IL-6, sIL-6R and CCL3 in COPD sputum.Methods59 COPD patients, 15 HNS and 15 S underwent sputum induction and processing with phosphate buffered saline to obtain supernatants for IL-6, sIL-6R and CCL3 analysis. Cytoslides were produced for differential cell counting and immunocytochemistry (COPD; n = 3) to determine cell type surface expression of the CCL3 receptors CCR5 and CCR1.ResultsCOPD patients expressed higher levels (p < 0.05) of sIL-6R and CCL3 compared to controls (sIL-6R medians pg/ml: COPD 166.4 vs S 101.1 vs HNS 96.4; CCL3 medians pg/ml: COPD 117.9 vs S 0 vs HNS 2.7). COPD sIL-6R levels were significantly correlated with sputum neutrophil (r = 0.5, p < 0.0001) and macrophage (r = 0.3, p = 0.01) counts. Immunocytochemical analysis revealed that CCR5 and CCR1 were exclusively expressed on airway macrophages.ConclusionEnhanced airway generation of sIL-6R may promote IL-6 trans-signaling in COPD. Associated upregulation of CCL3 may facilitate the recruitment of macrophages into the airways by ligation of CCR1 and CCR5.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-014-0103-4) contains supplementary material, which is available to authorized users.
Highlights
Chronic Obstructive Pulmonary Disease (COPD) arises due to an abnormal inflammatory response to inhaled noxious particles, such as cigarette smoke [1]
The COPD patients were significantly older than the control groups, the smoking pack year history was similar in COPD patients and S
We found that the CCL3 receptors CCR1 and CCR5 were exclusively expressed on sputum macrophages and not neutrophils, further implicating CCL3 in controlling macrophage chemotaxis in the airways of COPD patients
Summary
Chronic Obstructive Pulmonary Disease (COPD) arises due to an abnormal inflammatory response to inhaled noxious particles, such as cigarette smoke [1]. There are increased numbers of neutrophils and macrophages in the airways of COPD patients [2]. These cells organize the innate immune response, and contribute to inflammation through the secretion of cytokines, chemokines, elastolytic enzymes and reactive oxygen species [3,4]. IL-6 bound to sIL-6R forms a complex that binds to cell surface gp130 to initiate signal transduction, a process known as transsignaling [11]. COPD patients have increased numbers of macrophages and neutrophils in the lungs. Interleukin-6 (IL-6) trans-signaling via its soluble receptor sIL-6R, governs the influx of innate immune cells to inflammatory foci through regulation of the chemokine CCL3. We hypothesized that there would be enhanced levels of IL-6, sIL-6R and CCL3 in COPD sputum
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