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

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.

• Authors: Laura Keglowich, Michael Roth, Maria Philippova, Thérèse Resink, Gavin Tjin, Brian Oliver, Didier Lardinois, Sophie Dessus-Babus, Reinoud Gosens, Katrin Hostettler Haack, Michael Tamm, Peter Borger
• Journal: PloS one (PLoS One) Vol. 8 Issue 12 Pg. e81494 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24339939 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-(2-bromophenyl)-3-(7-cyano-3H-benzotriazol-4-yl)urea
• Chemokine CXCL1
• Chemokine CXCL5
• Chemokines, CXC
• Interleukin-8
• Ligands
• Phenylurea Compounds
• Receptors, Interleukin-8B
• Triazoles

Topics

• Adult
• Asthma (metabolism, pathology, physiopathology)
• Bronchi (pathology)
• Chemokine CXCL1 (metabolism)
• Chemokine CXCL5 (metabolism)
• Chemokines, CXC (metabolism)
• Female
• Humans
• Interleukin-8 (metabolism)
• Ligands
• Male
• Middle Aged
• Myocytes, Smooth Muscle (drug effects, metabolism)
• Neovascularization, Pathologic
• Phenylurea Compounds (pharmacology)
• Receptors, Interleukin-8B (antagonists & inhibitors, metabolism)
• Triazoles (pharmacology)
• Young Adult