Extracellular matrix in airway smooth muscle is associated with dynamics of airway function in asthma

被引:34
作者
Yick, C. Y. [1 ]
Ferreira, D. S. [2 ]
Annoni, R. [2 ]
von der Thusen, J. H. [3 ,4 ]
Kunst, P. W. [1 ]
Bel, E. H. [1 ]
Lutter, R. [1 ]
Mauad, T. [2 ]
Sterk, P. J. [1 ]
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Resp Med, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Sao Paulo, Dept Pathol, Sch Med, USP, Sao Paulo, Brazil
[3] Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands
[4] Royal Brompton & Harefield NHS Fdn Trust, Dept Histopathol, London, England
关键词
asthma; extracellular matrix; respiratory function tests; smooth muscle; PROTEINS; CELLS; WALL; PROLIFERATION; MODERATE;
D O I
10.1111/j.1398-9995.2011.02773.x
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Altered deposition of extracellular matrix (ECM) in the airway smooth muscle (ASM) layer as observed in asthma may influence ASM mechanical properties. We hypothesized that ECM in ASM is associated with airway function in asthma. First, we investigated the difference in ECM expression in ASM between asthma and controls. Second, we examined whether ECM expression is associated with bronchoconstriction and bronchodilation in vivo. Methods: Our cross-sectional study comprised 19 atopic mild asthma patients, 15 atopic and 12 nonatopic healthy subjects. Spirometry, methacholine responsiveness, deep-breath-induced bronchodilation (Delta R-rs) and bronchoscopy with endobronchial biopsies were performed. Positive staining of elastin, collagen I, III and IV, decorin, versican, fibronectin, laminin and tenascin in ASM was quantified as fractional area and mean density. Data were analysed using Pearson's or Spearman's correlation coefficient. Results: Extracellular matrix expression in ASM was not different between asthma and controls. In asthmatics, fractional area and mean density of collagen I and III were correlated with methacholine dose-response slope and DRrs, respectively (r = 0.71, P < 0.01; r = 0.60, P = 0.02). Furthermore, ASM collagen III and laminin in asthma were correlated with FEV1 reversibility (r = -0.65, P = 0.01; r = -0.54, P = 0.04). Conclusion: In asthma, ECM in ASM is related to the dynamics of airway function in the absence of differences in ECM expression between asthma and controls. This indicates that the ASM layer in its full composition is a major structural component in determining variable airways obstruction in asthma.
引用
收藏
页码:552 / 559
页数:8
相关论文
共 50 条
[21]   Airway smooth muscle as a target in asthma [J].
Hirst, SJ .
CLINICAL AND EXPERIMENTAL ALLERGY, 2000, 30 :54-59
[22]   AIRWAY REMODELING IN ASTHMA - ROLE OF AIRWAY SMOOTH-MUSCLE [J].
KNOX, AJ .
CLINICAL SCIENCE, 1994, 86 (06) :647-652
[23]   Potassium channels in airway smooth muscle and airway hyperreactivity in asthma [J].
Liu, XS ;
Xu, YJ .
CHINESE MEDICAL JOURNAL, 2005, 118 (07) :574-580
[24]   Extracellular matrix regulates human airway smooth muscle cell migration [J].
Parameswaran, K ;
Radford, K ;
Zuo, J ;
Janssen, LJ ;
O'Byrne, PM ;
Cox, PG .
EUROPEAN RESPIRATORY JOURNAL, 2004, 24 (04) :545-551
[25]   Impact of extracellular matrix and strain on proliferation of bovine airway smooth muscle [J].
Bonacci, JV ;
Harris, T ;
Stewart, AG .
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2003, 30 (5-6) :324-328
[26]   Extracellular matrix regulates enhanced eotaxin expression in asthmatic airway smooth muscle cells [J].
Chan, Vivien ;
Burgess, Janette K. ;
Ratoff, Jonathan C. ;
O'Connor, Brian J. ;
Greenough, Anne ;
Lee, Tak H. ;
Hirst, Stuart J. .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2006, 174 (04) :379-385
[27]   Connective tissue growth factor induces extracellular matrix in asthmatic airway smooth muscle [J].
Johnson, PRA ;
Burgess, JK ;
Ge, Q ;
Poniris, M ;
Boustany, S ;
Twigg, SM ;
Black, JL .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2006, 173 (01) :32-41
[28]   Origins of increased airway smooth muscle mass in asthma [J].
Berair, Rachid ;
Saunders, Ruth ;
Brightling, Christopher E. .
BMC MEDICINE, 2013, 11
[29]   Airway smooth muscle: a potential target for asthma therapy [J].
Dowell, Maria L. ;
Lavoie, Tera L. ;
Solway, Julian ;
Krishnan, Ramaswamy .
CURRENT OPINION IN PULMONARY MEDICINE, 2014, 20 (01) :66-72
[30]   Fibrocyte localization to the airway smooth muscle is a feature of asthma [J].
Saunders, Ruth ;
Siddiqui, Salman ;
Kaur, Davinder ;
Doe, Camille ;
Sutcliffe, Amanda ;
Hollins, Fay ;
Bradding, Peter ;
Wardlaw, Andrew ;
Brightling, Christopher E. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2009, 123 (02) :376-384