1. Bronchial smooth muscle cells of asthmatics promote angiogenesis through elevated secretion of CXC-chemokines (ENA-78, GRO-α, and IL-8).
- Author
-
Keglowich L, Roth M, Philippova M, Resink T, Tjin G, Oliver B, Lardinois D, Dessus-Babus S, Gosens R, Hostettler Haack K, Tamm M, and Borger P
- Subjects
- Adult, Asthma metabolism, Chemokine CXCL1 metabolism, Chemokine CXCL5 metabolism, Female, Humans, Interleukin-8 metabolism, Ligands, Male, Middle Aged, Myocytes, Smooth Muscle drug effects, Phenylurea Compounds pharmacology, Receptors, Interleukin-8B antagonists & inhibitors, Receptors, Interleukin-8B metabolism, Triazoles pharmacology, Young Adult, Asthma pathology, Asthma physiopathology, Bronchi pathology, Chemokines, CXC metabolism, Myocytes, Smooth Muscle metabolism, Neovascularization, Pathologic
- 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.
- Published
- 2013
- Full Text
- View/download PDF