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

被引:71
作者
Zanini, Andrea
Chetta, Alfredo
Saetta, Marina
Baraldo, Simonetta
D'Ippolito, Raffaele
Castagnaro, Antonio
Neri, Margherita
Olivieri, Dario
机构
[1] IRCCS, Fdn Salvatore Maugeri, Div Pneumol, Inst Rehabil Tradate, I-21049 Tradate, Italy
[2] Univ Parma, Sect Resp Dis, Dept Clin Sci, Parma, Italy
[3] Univ Padua, Sect Resp Dis, Dept Cardiothorac & Vasc Sci, I-35100 Padua, Italy
关键词
mast cells; bronchial asthma; vascular remodeling;
D O I
10.1016/j.jaci.2007.04.021
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: There is increasing evidence to support a role for total mast cells (MCTOT) 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 (MCTC) in microvasculature changes. Objective: We sought to assess the role of MCTC 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, MCTOT, and MCTC. Results: Compared with those from healthy subjects, endobronchial biopsy specimens from asthmatic patients showed increased numbers of MCTOT and MCTC 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 MCTC 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 MCTC were a relevant cellular source of VEGF. Finally, a 6-week treatment with inhaled fluticasone propionate was able to reduce MCTC numbers. Conclusion: MCTC can play a role in the vascular component of airway remodeling in asthma, possibly through induction of VEGF. Clinical implications: Specific targeting of MCTC might be a toot for treating vascular remodeling in asthma.
引用
收藏
页码:329 / 333
页数:5
相关论文
共 34 条
[1]  
[Anonymous], 1987, AM REV RESPIR DIS, V136, P225
[2]   Relationship of small airway chymase-positive mast cells and lung function in severe asthma [J].
Balzar, S ;
Chu, HW ;
Strand, M ;
Wenzel, S .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2005, 171 (05) :431-439
[3]   Prednisolone treatment in asthma - Reduction in the numbers of eosinophils, T cells, tryptase-only positive mast cells, and modulation of IL-4, IL-5, and interferon-gamma cytokine gene expression within the bronchial mucosa [J].
Bentley, AM ;
Hamid, Q ;
Robinson, DS ;
Schotman, E ;
Meng, Q ;
Assoufi, B ;
Kay, AB ;
Durham, SR .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1996, 153 (02) :551-556
[4]  
Berger P, 1999, CLIN EXP ALLERGY, V29, P804
[5]   Human mast cells stimulate vascular tribe formation - Tryptase is a novel, potent angiogenic factor [J].
Blair, RJ ;
Meng, H ;
Marchese, MJ ;
Ren, SL ;
Schwartz, LB ;
Tonnesen, MG ;
Gruber, BL .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (11) :2691-2700
[6]   Asthma - From bronchoconstriction to airways inflammation and remodeling [J].
Bousquet, J ;
Jeffery, PK ;
Busse, WW ;
Johnson, M ;
Vignola, AM .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2000, 161 (05) :1720-1745
[7]   Mast-cell infiltration of airway smooth muscle in asthma [J].
Brightling, CE ;
Bradding, P ;
Symon, FA ;
Holgate, ST ;
Wardlaw, AJ ;
Pavord, ID .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (22) :1699-1705
[8]   IMMUNOHISTOCHEMISTRY ON RESIN SECTIONS - A COMPARISON OF RESIN EMBEDDING TECHNIQUES FOR SMALL MUCOSAL BIOPSIES [J].
BRITTEN, KM ;
HOWARTH, PH ;
ROCHE, WR .
BIOTECHNIC & HISTOCHEMISTRY, 1993, 68 (05) :271-280
[9]   Airways remodeling is a distinctive feature of asthma and is related to severity of disease [J].
Chetta, A ;
Foresi, A ;
DelDonno, M ;
Bertorelli, G ;
Pesci, A ;
Olivieri, D .
CHEST, 1997, 111 (04) :852-857
[10]   Vascular endothelial growth factor up-regulation and bronchial wall remodelling in asthma [J].
Chetta, A ;
Zanini, A ;
Foresi, A ;
D'Ippolito, R ;
Tipa, A ;
Castagnaro, A ;
Baraldo, S ;
Neri, M ;
Saetta, M ;
Olivieri, D .
CLINICAL AND EXPERIMENTAL ALLERGY, 2005, 35 (11) :1437-1442