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Chymase-positive mast cells play a role in the vascular component of airway remodeling in asthma
Authors:Zanini Andrea  Chetta Alfredo  Saetta Marina  Baraldo Simonetta  D'Ippolito Raffaele  Castagnaro Antonio  Neri Margherita  Olivieri Dario
Institution:Salvatore Maugeri Foundation, Division of Pneumology, IRCCS Rehabilitation Institute of Tradate, Tradate, Italy. azanini@fsm.it
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.
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