COPD monocytes demonstrate impaired migratory ability
Abstract Background Increased lung macrophage numbers in COPD may arise from upregulation of blood monocyte recruitment into the lungs. CCR5 is a monocyte chemokine receptor regulated by interleukin-6 (IL-6); the concentration of CCR5 ligands are known to be elevated in COPD lungs. The objective of...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-05-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12931-017-0569-y |
| _version_ | 1818846667794808832 |
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| author | Arjun K Ravi Jonathan Plumb Rosemary Gaskell Sarah Mason Caroline S Broome George Booth Matthew Catley Jørgen Vestbo Dave Singh |
| author_facet | Arjun K Ravi Jonathan Plumb Rosemary Gaskell Sarah Mason Caroline S Broome George Booth Matthew Catley Jørgen Vestbo Dave Singh |
| author_sort | Arjun K Ravi |
| collection | DOAJ |
| description | Abstract Background Increased lung macrophage numbers in COPD may arise from upregulation of blood monocyte recruitment into the lungs. CCR5 is a monocyte chemokine receptor regulated by interleukin-6 (IL-6); the concentration of CCR5 ligands are known to be elevated in COPD lungs. The objective of this study was to investigate mechanisms of monocyte recruitment to the lung in COPD, including the role of CCR5 signalling. Methods Ninety one COPD patients, 29 smokers (S) and 37 non-smokers (NS) underwent sputum induction, plasma sampling (to measure IL-6 and soluble IL-6 receptor [sIL-6R] by immunoassay), monocyte characterization (by flow cytometry) and monocyte isolation for cell migration and quantitative polymerase chain reaction studies. Lung tissue was used for immunohistochemistry. Results Plasma IL-6 and sIL-6R levels were increased in COPD. Greater proportions of COPD CD14++CD16+ monocytes expressed CCR5 compared to controls. Monocyte stimulation with IL-6 and sIL-6R increased CCR5 gene expression. COPD monocytes demonstrated impaired migration towards sputum supernatant compared to NS (% migration, 4.4 vs 11.5, respectively; p < 0.05). Pulmonary microvessels showed reduced monocyte recruitment (% marginated cells) in COPD compared to NS, (9.3% vs 83.1%, respectively). The proportion of replicating Ki67+ alveolar macrophages was reduced in COPD compared to NS. All alveolar macrophages from COPD and S expressed the anti-apoptosis marker BCL2; this protein was not present in non-smokers or COPD ex-smokers. Conclusion COPD monocytes show decreased migratory ability despite increased CCR5 expression. Increased COPD lung macrophage numbers may be due to delayed apoptosis. |
| first_indexed | 2024-12-19T05:49:12Z |
| format | Article |
| id | doaj.art-61a222d4ffaa4dd494c89a0113503076 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-12-19T05:49:12Z |
| publishDate | 2017-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-61a222d4ffaa4dd494c89a01135030762022-12-21T20:33:41ZengBMCRespiratory Research1465-993X2017-05-0118111210.1186/s12931-017-0569-yCOPD monocytes demonstrate impaired migratory abilityArjun K Ravi0Jonathan Plumb1Rosemary Gaskell2Sarah Mason3Caroline S Broome4George Booth5Matthew Catley6Jørgen Vestbo7Dave Singh8NIHR Respiratory and Allergy Clinical Research Facility, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, University of ManchesterNIHR Respiratory and Allergy Clinical Research Facility, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, University of ManchesterNIHR Respiratory and Allergy Clinical Research Facility, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, University of ManchesterNIHR Respiratory and Allergy Clinical Research Facility, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, University of ManchesterNIHR Respiratory and Allergy Clinical Research Facility, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, University of ManchesterNIHR Respiratory and Allergy Clinical Research Facility, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, University of ManchesterUCB, SloughNIHR Respiratory and Allergy Clinical Research Facility, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, University of ManchesterNIHR Respiratory and Allergy Clinical Research Facility, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, University of ManchesterAbstract Background Increased lung macrophage numbers in COPD may arise from upregulation of blood monocyte recruitment into the lungs. CCR5 is a monocyte chemokine receptor regulated by interleukin-6 (IL-6); the concentration of CCR5 ligands are known to be elevated in COPD lungs. The objective of this study was to investigate mechanisms of monocyte recruitment to the lung in COPD, including the role of CCR5 signalling. Methods Ninety one COPD patients, 29 smokers (S) and 37 non-smokers (NS) underwent sputum induction, plasma sampling (to measure IL-6 and soluble IL-6 receptor [sIL-6R] by immunoassay), monocyte characterization (by flow cytometry) and monocyte isolation for cell migration and quantitative polymerase chain reaction studies. Lung tissue was used for immunohistochemistry. Results Plasma IL-6 and sIL-6R levels were increased in COPD. Greater proportions of COPD CD14++CD16+ monocytes expressed CCR5 compared to controls. Monocyte stimulation with IL-6 and sIL-6R increased CCR5 gene expression. COPD monocytes demonstrated impaired migration towards sputum supernatant compared to NS (% migration, 4.4 vs 11.5, respectively; p < 0.05). Pulmonary microvessels showed reduced monocyte recruitment (% marginated cells) in COPD compared to NS, (9.3% vs 83.1%, respectively). The proportion of replicating Ki67+ alveolar macrophages was reduced in COPD compared to NS. All alveolar macrophages from COPD and S expressed the anti-apoptosis marker BCL2; this protein was not present in non-smokers or COPD ex-smokers. Conclusion COPD monocytes show decreased migratory ability despite increased CCR5 expression. Increased COPD lung macrophage numbers may be due to delayed apoptosis.http://link.springer.com/article/10.1186/s12931-017-0569-yCOPDMonocytesCCR5ChemotaxisInterleukin-6 |
| spellingShingle | Arjun K Ravi Jonathan Plumb Rosemary Gaskell Sarah Mason Caroline S Broome George Booth Matthew Catley Jørgen Vestbo Dave Singh COPD monocytes demonstrate impaired migratory ability Respiratory Research COPD Monocytes CCR5 Chemotaxis Interleukin-6 |
| title | COPD monocytes demonstrate impaired migratory ability |
| title_full | COPD monocytes demonstrate impaired migratory ability |
| title_fullStr | COPD monocytes demonstrate impaired migratory ability |
| title_full_unstemmed | COPD monocytes demonstrate impaired migratory ability |
| title_short | COPD monocytes demonstrate impaired migratory ability |
| title_sort | copd monocytes demonstrate impaired migratory ability |
| topic | COPD Monocytes CCR5 Chemotaxis Interleukin-6 |
| url | http://link.springer.com/article/10.1186/s12931-017-0569-y |
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