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Increased levels of soluble interleukin-6 receptor and CCL3 in COPD sputum

BACKGROUND: 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 woul...

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Autores principales: Ravi, Arjun K, Khurana, Shruti, Lemon, Jonathan, Plumb, Jonathan, Booth, George, Healy, Louise, Catley, Matthew, Vestbo, Jørgen, Singh, Dave
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156958/
https://www.ncbi.nlm.nih.gov/pubmed/25183374
http://dx.doi.org/10.1186/s12931-014-0103-4
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author Ravi, Arjun K
Khurana, Shruti
Lemon, Jonathan
Plumb, Jonathan
Booth, George
Healy, Louise
Catley, Matthew
Vestbo, Jørgen
Singh, Dave
author_facet Ravi, Arjun K
Khurana, Shruti
Lemon, Jonathan
Plumb, Jonathan
Booth, George
Healy, Louise
Catley, Matthew
Vestbo, Jørgen
Singh, Dave
author_sort Ravi, Arjun K
collection PubMed
description BACKGROUND: 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. METHODS: 59 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. RESULTS: COPD 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. CONCLUSION: Enhanced 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 MATERIAL: The online version of this article (doi:10.1186/s12931-014-0103-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-41569582014-09-08 Increased levels of soluble interleukin-6 receptor and CCL3 in COPD sputum Ravi, Arjun K Khurana, Shruti Lemon, Jonathan Plumb, Jonathan Booth, George Healy, Louise Catley, Matthew Vestbo, Jørgen Singh, Dave Respir Res Research BACKGROUND: 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. METHODS: 59 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. RESULTS: COPD 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. CONCLUSION: Enhanced 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 MATERIAL: The online version of this article (doi:10.1186/s12931-014-0103-4) contains supplementary material, which is available to authorized users. BioMed Central 2014-09-04 2014 /pmc/articles/PMC4156958/ /pubmed/25183374 http://dx.doi.org/10.1186/s12931-014-0103-4 Text en © Ravi et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Research
Ravi, Arjun K
Khurana, Shruti
Lemon, Jonathan
Plumb, Jonathan
Booth, George
Healy, Louise
Catley, Matthew
Vestbo, Jørgen
Singh, Dave
Increased levels of soluble interleukin-6 receptor and CCL3 in COPD sputum
title Increased levels of soluble interleukin-6 receptor and CCL3 in COPD sputum
title_full Increased levels of soluble interleukin-6 receptor and CCL3 in COPD sputum
title_fullStr Increased levels of soluble interleukin-6 receptor and CCL3 in COPD sputum
title_full_unstemmed Increased levels of soluble interleukin-6 receptor and CCL3 in COPD sputum
title_short Increased levels of soluble interleukin-6 receptor and CCL3 in COPD sputum
title_sort increased levels of soluble interleukin-6 receptor and ccl3 in copd sputum
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156958/
https://www.ncbi.nlm.nih.gov/pubmed/25183374
http://dx.doi.org/10.1186/s12931-014-0103-4
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