Neutrophils from Patients with Primary Ciliary Dyskinesia Display Reduced Chemotaxis to CXCR2 Ligands
Primary ciliary dyskinesia (PCD), cystic fibrosis (CF), and chronic obstructive airway disease are characterized by neutrophilic inflammation in the lungs. In CF and chronic obstructive airway disease, improper functioning of neutrophils has been demonstrated. We hypothesized that the pulmonary dama...
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Frontiers Media S.A.
2017-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01126/full |
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| author | Maaike Cockx Mieke Gouwy Véronique Godding Kris De Boeck Jo Van Damme Mieke Boon Sofie Struyf |
| author_facet | Maaike Cockx Mieke Gouwy Véronique Godding Kris De Boeck Jo Van Damme Mieke Boon Sofie Struyf |
| author_sort | Maaike Cockx |
| collection | DOAJ |
| description | Primary ciliary dyskinesia (PCD), cystic fibrosis (CF), and chronic obstructive airway disease are characterized by neutrophilic inflammation in the lungs. In CF and chronic obstructive airway disease, improper functioning of neutrophils has been demonstrated. We hypothesized that the pulmonary damage in PCD might be aggravated by abnormal functioning neutrophils either as a primary consequence of the PCD mutation or secondary to chronic inflammation. We analyzed chemotactic responses and chemoattractant receptor expression profiles of peripheral blood neutrophils from 36 patients with PCD, 21 healthy children and 19 healthy adults. We stimulated peripheral blood monocytes from patients and healthy controls and measured CXCL8 and IL-1β production with ELISA. PCD neutrophils displayed reduced migration toward CXCR2 ligands (CXCL5 and CXCL8) in the shape change, microchamber and microslide chemotaxis assays, whereas leukotriene B4 and complement component 5a chemotactic responses were not significantly different. The reduced response to CXCL8 was observed in all subgroups of patients with PCD (displaying either normal ultrastructure, dynein abnormalities or central pair deficiencies) and correlated with lung function. CXCR2 was downregulated in about 65% of the PCD patients, suggestive for additional mechanisms causing CXCR2 impairment. After treatment with the TLR ligands lipopolysaccharide and peptidoglycan, PCD monocytes produced more CXCL8 and IL-1β compared to controls. Moreover, PCD monocytes also responded stronger to IL-1β stimulation in terms of CXCL8 production. In conclusion, we revealed a potential link between CXCR2 and its ligand CXCL8 and the pathogenesis of PCD. |
| first_indexed | 2024-12-11T00:18:00Z |
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| id | doaj.art-804784acd24a4abcb93194a7b26fd2bb |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T00:18:00Z |
| publishDate | 2017-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-804784acd24a4abcb93194a7b26fd2bb2022-12-22T01:27:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-09-01810.3389/fimmu.2017.01126291071Neutrophils from Patients with Primary Ciliary Dyskinesia Display Reduced Chemotaxis to CXCR2 LigandsMaaike Cockx0Mieke Gouwy1Véronique Godding2Kris De Boeck3Jo Van Damme4Mieke Boon5Sofie Struyf6Laboratory of Molecular Immunology, Department of Microbiology and Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, BelgiumLaboratory of Molecular Immunology, Department of Microbiology and Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, BelgiumUnité de Pneumologie Pédiatrique et Mucoviscidose, Clinique Universitaire Saint-Luc UCL Brussels, Brussels, BelgiumPediatric Pulmonology and Cystic Fibrosis Unit, Department of Pediatrics, University Hospitals Leuven, Leuven, BelgiumLaboratory of Molecular Immunology, Department of Microbiology and Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, BelgiumPediatric Pulmonology and Cystic Fibrosis Unit, Department of Pediatrics, University Hospitals Leuven, Leuven, BelgiumLaboratory of Molecular Immunology, Department of Microbiology and Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, BelgiumPrimary ciliary dyskinesia (PCD), cystic fibrosis (CF), and chronic obstructive airway disease are characterized by neutrophilic inflammation in the lungs. In CF and chronic obstructive airway disease, improper functioning of neutrophils has been demonstrated. We hypothesized that the pulmonary damage in PCD might be aggravated by abnormal functioning neutrophils either as a primary consequence of the PCD mutation or secondary to chronic inflammation. We analyzed chemotactic responses and chemoattractant receptor expression profiles of peripheral blood neutrophils from 36 patients with PCD, 21 healthy children and 19 healthy adults. We stimulated peripheral blood monocytes from patients and healthy controls and measured CXCL8 and IL-1β production with ELISA. PCD neutrophils displayed reduced migration toward CXCR2 ligands (CXCL5 and CXCL8) in the shape change, microchamber and microslide chemotaxis assays, whereas leukotriene B4 and complement component 5a chemotactic responses were not significantly different. The reduced response to CXCL8 was observed in all subgroups of patients with PCD (displaying either normal ultrastructure, dynein abnormalities or central pair deficiencies) and correlated with lung function. CXCR2 was downregulated in about 65% of the PCD patients, suggestive for additional mechanisms causing CXCR2 impairment. After treatment with the TLR ligands lipopolysaccharide and peptidoglycan, PCD monocytes produced more CXCL8 and IL-1β compared to controls. Moreover, PCD monocytes also responded stronger to IL-1β stimulation in terms of CXCL8 production. In conclusion, we revealed a potential link between CXCR2 and its ligand CXCL8 and the pathogenesis of PCD.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01126/fullchemokineschemotaxiscytokinesIL-1inflammationneutrophils |
| spellingShingle | Maaike Cockx Mieke Gouwy Véronique Godding Kris De Boeck Jo Van Damme Mieke Boon Sofie Struyf Neutrophils from Patients with Primary Ciliary Dyskinesia Display Reduced Chemotaxis to CXCR2 Ligands Frontiers in Immunology chemokines chemotaxis cytokines IL-1 inflammation neutrophils |
| title | Neutrophils from Patients with Primary Ciliary Dyskinesia Display Reduced Chemotaxis to CXCR2 Ligands |
| title_full | Neutrophils from Patients with Primary Ciliary Dyskinesia Display Reduced Chemotaxis to CXCR2 Ligands |
| title_fullStr | Neutrophils from Patients with Primary Ciliary Dyskinesia Display Reduced Chemotaxis to CXCR2 Ligands |
| title_full_unstemmed | Neutrophils from Patients with Primary Ciliary Dyskinesia Display Reduced Chemotaxis to CXCR2 Ligands |
| title_short | Neutrophils from Patients with Primary Ciliary Dyskinesia Display Reduced Chemotaxis to CXCR2 Ligands |
| title_sort | neutrophils from patients with primary ciliary dyskinesia display reduced chemotaxis to cxcr2 ligands |
| topic | chemokines chemotaxis cytokines IL-1 inflammation neutrophils |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01126/full |
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