title: 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.
  
  
  CONCLUSIONS
  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: Pulmonary Cell Research & Signal Transduction, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors: Laura
authors: L
authors: Keglowich
authors: Michael
authors: M
authors: Roth
authors: Maria
authors: M
authors: Philippova
authors: Thérèse
authors: T
authors: Resink
authors: Gavin
authors: G
authors: Tjin
authors: Brian
authors: B
authors: Oliver
authors: Didier
authors: D
authors: Lardinois
authors: Sophie
authors: S
authors: Dessus-Babus
authors: Reinoud
authors: R
authors: Gosens
authors: Katrin
authors: K
authors: Hostettler Haack
authors: Michael
authors: M
authors: Tamm
authors: Peter
authors: P
authors: Borger
mesh_terms: D000328:Adult; D001249:Asthma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D001980:Bronchi / Q000473:pathology*; D054360:Chemokine CXCL1 / Q000378:metabolism; D054365:Chemokine CXCL5 / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008024:Ligands; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D010671:Phenylurea Compounds / Q000494:pharmacology; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology; D055815:Young Adult
chemical_list: C549500:1-(2-bromophenyl)-3-(7-cyano-3H-benzotriazol-4-yl)urea; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D016209:Interleukin-8; D008024:Ligands; D010671:Phenylurea Compounds; D023063:Receptors, Interleukin-8B; D014230:Triazoles