Bronchial smooth muscle cells of asthmatics promote angiogenesis through elevated secretion of CXC-chemokines (ENA-78, GRO-α, and IL-8)

Keglowich, L; Roth, M; Philippova, M; Resink, T; Tjin, G; Oliver, B; Lardinois, D; Dessus-Babus, S; Gosens, R; Haack, KH; Tamm, M; Borger, P

Bronchial smooth muscle cells of asthmatics promote angiogenesis through elevated secretion of CXC-chemokines (ENA-78, GRO-α, and IL-8)

Keglowich, L Roth, M Philippova, M Resink, T Tjin, G Oliver, B

Lardinois, D Dessus-Babus, S Gosens, R Haack, KH Tamm, M Borger, P

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Publication Type:: Journal Article
Citation:: PLoS ONE, 2013, 8 (12)
Issue Date:: 2013-12-05

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Field	Value	Language
dc.contributor.author	Keglowich, L	en_US
dc.contributor.author	Roth, M	en_US
dc.contributor.author	Philippova, M	en_US
dc.contributor.author	Resink, T	en_US
dc.contributor.author	Tjin, G	en_US
dc.contributor.author	Oliver, B https://orcid.org/0000-0002-7122-9262	en_US
dc.contributor.author	Lardinois, D	en_US
dc.contributor.author	Dessus-Babus, S	en_US
dc.contributor.author	Gosens, R	en_US
dc.contributor.author	Haack, KH	en_US
dc.contributor.author	Tamm, M	en_US
dc.contributor.author	Borger, P	en_US
dc.date.available	2013-10-14	en_US
dc.date.issued	2013-12-05	en_US
dc.identifier.citation	PLoS ONE, 2013, 8 (12)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/41771
dc.description.abstract	Background: Airway wall remodelling is a key pathology of asthma. It includes thickening of the airway wall, hypertrophy and hyperplasia of bronchial smooth muscle cells (BSMC), as well as an increased vascularity of the sub-epithelial cell layer BSMC are known to be the effector cells of bronchoconstriction, but they are increasingly recognized as an important source of inflammatory mediators and angiogenic factors. Objective: To compare the angiogenic potential of BSMC of asthmatic and non-asthmatic patients and to identify asthma-specific angiogenic factors Methods: Primary BSMC were isolated from human airway tissue of asthmatic and non-asthmatic patients. Conditioned medium (CM) collected from BSMC isolates was tested for angiogenic capacity using the endothelial cell (EC)-spheroid in vitro angiogenesis assay. Angiogenic factors in CM were quantified using a human angiogenesis antibody array and enzyme linked immunosorbent assay. Results: Induction of sprout outgrowth from EC-spheroids by CM of BSMC obtained from asthma patients was increased compared with CM of control BSMC (twofold, p < 0.001). Levels of ENA-78, GRO-α and IL-8 were significantly elevated in CM of BSMC from asthma patients (p < 0.05 vs. non-asthmatic patients). SB 265610, a competitive antagonist of chemokine (CXC-motif) receptor 2 CXCR2), attenuated the increased sprout outgrowth induced by CM of asthma patient-derived BSMC. Conclusions: BSMC isolated from asthma patients exhibit increased angiogenic potential. This effect is mediated through the CXCR2 ligands (ENA78, GRO-α and IL-8) produced by BSMC Implications: CXCR2 ligands may play a decisive role in directing the neovascularization in the sub-epithelial cell layers of the lungs of asthma patients Counteracting the CXCR2 mediated neovascularization by pharmaceutical compounds may represent a novel strategy to reduce airway remodelling in asthma. © 2013 Keglowich et al.	en_US
dc.relation.ispartof	PLoS ONE	en_US
dc.relation.isbasedon	10.1371/journal.pone.0081494	en_US
dc.subject.classification	General Science & Technology	en_US
dc.subject.mesh	Bronchi	en_US
dc.subject.mesh	Myocytes, Smooth Muscle	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Asthma	en_US
dc.subject.mesh	Neovascularization, Pathologic	en_US
dc.subject.mesh	Phenylurea Compounds	en_US
dc.subject.mesh	Triazoles	en_US
dc.subject.mesh	Receptors, Interleukin-8B	en_US
dc.subject.mesh	Chemokines, CXC	en_US
dc.subject.mesh	Interleukin-8	en_US
dc.subject.mesh	Ligands	en_US
dc.subject.mesh	Adult	en_US
dc.subject.mesh	Middle Aged	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Chemokine CXCL1	en_US
dc.subject.mesh	Chemokine CXCL5	en_US
dc.subject.mesh	Young Adult	en_US
dc.title	Bronchial smooth muscle cells of asthmatics promote angiogenesis through elevated secretion of CXC-chemokines (ENA-78, GRO-α, and IL-8)	en_US
dc.type	Journal Article
utslib.citation.volume	12	en_US
utslib.citation.volume	8	en_US
utslib.for	1103 Clinical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	12	en_US
pubs.publication-status	Published	en_US
pubs.volume	8	en_US

Abstract:

Background: Airway wall remodelling is a key pathology of asthma. It includes thickening of the airway wall, hypertrophy and hyperplasia of bronchial smooth muscle cells (BSMC), as well as an increased vascularity of the sub-epithelial cell layer BSMC are known to be the effector cells of bronchoconstriction, but they are increasingly recognized as an important source of inflammatory mediators and angiogenic factors. Objective: To compare the angiogenic potential of BSMC of asthmatic and non-asthmatic patients and to identify asthma-specific angiogenic factors Methods: Primary BSMC were isolated from human airway tissue of asthmatic and non-asthmatic patients. Conditioned medium (CM) collected from BSMC isolates was tested for angiogenic capacity using the endothelial cell (EC)-spheroid in vitro angiogenesis assay. Angiogenic factors in CM were quantified using a human angiogenesis antibody array and enzyme linked immunosorbent assay. Results: Induction of sprout outgrowth from EC-spheroids by CM of BSMC obtained from asthma patients was increased compared with CM of control BSMC (twofold, p < 0.001). Levels of ENA-78, GRO-α and IL-8 were significantly elevated in CM of BSMC from asthma patients (p < 0.05 vs. non-asthmatic patients). SB 265610, a competitive antagonist of chemokine (CXC-motif) receptor 2 CXCR2), attenuated the increased sprout outgrowth induced by CM of asthma patient-derived BSMC. Conclusions: BSMC isolated from asthma patients exhibit increased angiogenic potential. This effect is mediated through the CXCR2 ligands (ENA78, GRO-α and IL-8) produced by BSMC Implications: CXCR2 ligands may play a decisive role in directing the neovascularization in the sub-epithelial cell layers of the lungs of asthma patients Counteracting the CXCR2 mediated neovascularization by pharmaceutical compounds may represent a novel strategy to reduce airway remodelling in asthma. © 2013 Keglowich et al.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/28521