Chymase-positive mast cells play a role in the vascular component of airway remodeling in asthma

J Allergy Clin Immunol. 2007 Aug;120(2):329-33. doi: 10.1016/j.jaci.2007.04.021. Epub 2007 Jun 7.

Abstract

Background: There is increasing evidence to support a role for total mast cells (MC(TOT)) in the vascular component of airway remodeling in asthma. On the contrary, up to now, no study has addressed the role of chymase-positive mast cells (MC(TC)) in microvasculature changes.

Objective: We sought to assess the role of MC(TC) in the vascular component of airway remodeling in asthma.

Methods: We recruited 8 patients with mild-to-moderate asthma and 8 healthy volunteers as a control group. Fiberoptic bronchoscopy with endobronchial biopsy was successfully performed in all subjects. Immunostaining was performed for quantification of vessels, vascular endothelial growth factor (VEGF)-positive cells, MC(TOT), and MC(TC).

Results: Compared with those from healthy subjects, endobronchial biopsy specimens from asthmatic patients showed increased numbers of MC(TOT) and MC(TC) and VEGF(+) cells (P < .05). In asthmatic patients the number of vessels and the vascular area was also greater than in healthy subjects (P < .05). Additionally, in asthmatic patients the number of MC(TC) was significantly related to the vascular area (r(s) = 0.74, P < .01) and to the number of VEGF(+) cells (r(s) = 0.78, P < .01). Moreover, a colocalization study revealed that MC(TC) were a relevant cellular source of VEGF. Finally, a 6-week treatment with inhaled fluticasone propionate was able to reduce MC(TC) numbers.

Conclusion: MC(TC) can play a role in the vascular component of airway remodeling in asthma, possibly through induction of VEGF.

Clinical implications: Specific targeting of MC(TC) might be a tool for treating vascular remodeling in asthma.

MeSH terms

  • Adult
  • Androstadienes / administration & dosage
  • Androstadienes / therapeutic use
  • Asthma / drug therapy
  • Asthma / pathology
  • Asthma / physiopathology*
  • Blood Vessels / physiopathology
  • Bronchi / blood supply*
  • Bronchi / pathology
  • Bronchi / physiopathology*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / therapeutic use
  • Bronchoscopy
  • Cell Count
  • Chymases / metabolism*
  • Drug Administration Schedule
  • Female
  • Fiber Optic Technology
  • Fluticasone
  • Humans
  • Male
  • Mast Cells / drug effects
  • Mast Cells / enzymology*
  • Mast Cells / metabolism
  • Mast Cells / pathology
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Androstadienes
  • Bronchodilator Agents
  • Vascular Endothelial Growth Factor A
  • Fluticasone
  • Chymases