Bronchial Smooth Muscle Cells of Asthmatics Promote Angiogenesis through Elevated Secretion of CXC-Chemokines (ENA-78, GRO-α, and IL-8)

被引：41

作者：

Keglowich, Laura ^{[1
]}

Roth, Michael ^{[2
]}

Philippova, Maria ^{[1
]}

Resink, Therese ^{[1
]}

Tjin, Gavin ^{[3
,4
]}

Oliver, Brian ^{[3
,4
]}

Lardinois, Didier ^{[5
]}

Dessus-Babus, Sophie ^{[6
]}

Gosens, Reinoud ^{[7
]}

Haack, Katrin Hostettler ^{[1
,2
]}

Tamm, Michael ^{[1
,2
]}

Borger, Peter ^{[1
]}

机构：

[1] Univ Basel, Dept Biomed, Basel, Switzerland

[2] Univ Basel Hosp, Dept Pneumol, CH-4031 Basel, Switzerland

[3] Univ Sydney, Dept Pharmacol, Sydney Med Sch, Sydney, NSW 2006, Australia

[4] Univ Sydney, Woolcock Inst Med Res, Sydney, NSW 2006, Australia

[5] Univ Basel Hosp, Dept Thorac Surg, CH-4031 Basel, Switzerland

[6] Friedrich Miescher Inst Biomed Res, Basel, Switzerland

[7] Univ Groningen, Dept Mol Pharmacol, Groningen, Netherlands

来源：

PLOS ONE | 2013年 / 8卷 / 12期

基金：

瑞士国家科学基金会;

关键词：

INDUCED SPUTUM; C/EBP-ALPHA; EXPRESSION; AIRWAYS; VEGF; PROLIFERATION; VASCULARITY; ANTAGONISTS; SPHEROIDS; CHILDREN;

D O I：

10.1371/journal.pone.0081494

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-alpha 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-alpha 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.

引用

页数：12

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[1] A comparative study of two angiogenic factors - Vascular endothelial growth factor and angiogenin in induced sputum from asthmatic children in acute attack [J].