BACKGROUND: Asthma likely involves an active injury and repair process, including components such as neutrophils and matrix metalloproteinase 9 (MMP-9). Although MMP-9 is increased in lavage fluid and sputum in patients with asthma, controversy exists as to the role of tissue MMP-9. OBJECTIVE: The purpose of this study was to determine whether increases in submucosal cellular MMP-9, matrix MMP-9 (subepithelial basement membrane [SBM]), or both would be associated with severe asthma, neutrophilic inflammation, and wound repair. METHODS: Immunohistochemical staining and analyses of MMP-9, inflammatory cells, transforming growth factor beta, and collagen I were performed in endobronchial biopsy specimens, bronchoalveolar lavage fluid, or both from 38 patients with severe asthma and compared with results in 10 patients with mild asthma, 8 patients with moderate asthma, and 10 healthy control subjects. RESULTS: A significantly greater proportion of patients with severe asthma demonstrated MMP-9 staining of the SBM than control subjects (P =.02). Bronchoalveolar lavage MMP-9 levels were also increased in patients with severe asthma (P =.0004). The numbers of submucosal neutrophils and macrophages, but not eosinophils, were significantly higher in asthmatic individuals with MMP-9 staining of the SBM (P =.004 and P =.01, respectively). However, the presence of SBM MMP-9 was associated with a high correlation between lavage and tissue eosinophils (r = 0.58, P =.009). Although the SBM thickness did not differ between groups, higher numbers of transforming growth factor beta-positive cells were seen in subjects with SBM MMP-9 staining. Pulmonary function was significantly lower in those asthmatic subjects with SBM staining. CONCLUSIONS: These results suggest that localized tissue MMP-9 might play an important role in wound repair and cell trafficking.
BACKGROUND:Asthma likely involves an active injury and repair process, including components such as neutrophils and matrix metalloproteinase 9 (MMP-9). Although MMP-9 is increased in lavage fluid and sputum in patients with asthma, controversy exists as to the role of tissue MMP-9. OBJECTIVE: The purpose of this study was to determine whether increases in submucosal cellular MMP-9, matrix MMP-9 (subepithelial basement membrane [SBM]), or both would be associated with severe asthma, neutrophilic inflammation, and wound repair. METHODS: Immunohistochemical staining and analyses of MMP-9, inflammatory cells, transforming growth factor beta, and collagen I were performed in endobronchial biopsy specimens, bronchoalveolar lavage fluid, or both from 38 patients with severe asthma and compared with results in 10 patients with mild asthma, 8 patients with moderate asthma, and 10 healthy control subjects. RESULTS: A significantly greater proportion of patients with severe asthma demonstrated MMP-9 staining of the SBM than control subjects (P =.02). Bronchoalveolar lavage MMP-9 levels were also increased in patients with severe asthma (P =.0004). The numbers of submucosal neutrophils and macrophages, but not eosinophils, were significantly higher in asthmatic individuals with MMP-9 staining of the SBM (P =.004 and P =.01, respectively). However, the presence of SBMMMP-9 was associated with a high correlation between lavage and tissue eosinophils (r = 0.58, P =.009). Although the SBM thickness did not differ between groups, higher numbers of transforming growth factor beta-positive cells were seen in subjects with SBMMMP-9 staining. Pulmonary function was significantly lower in those asthmatic subjects with SBM staining. CONCLUSIONS: These results suggest that localized tissue MMP-9 might play an important role in wound repair and cell trafficking.
Authors: Prescott G Woodruff; Maarten van den Berge; Richard C Boucher; Christopher Brightling; Esteban G Burchard; Stephanie A Christenson; MeiLan K Han; Michael J Holtzman; Monica Kraft; David A Lynch; Fernando D Martinez; Helen K Reddel; Don D Sin; George R Washko; Sally E Wenzel; Antonello Punturieri; Michelle M Freemer; Robert A Wise Journal: Am J Respir Crit Care Med Date: 2017-08-01 Impact factor: 21.405
Authors: Stanley J Szefler; Sally Wenzel; Robert Brown; Serpil C Erzurum; John V Fahy; Robert G Hamilton; John F Hunt; Hirohito Kita; Andrew H Liu; Reynold A Panettieri; Robert P Schleimer; Michael Minnicozzi Journal: J Allergy Clin Immunol Date: 2012-03 Impact factor: 10.793
Authors: H Matsumoto; A Niimi; M Takemura; T Ueda; M Minakuchi; R Tabuena; K Chin; T Mio; Y Ito; S Muro; T Hirai; S Morita; S Fukuhara; M Mishima Journal: Thorax Date: 2005-04 Impact factor: 9.139