The outer wall of small airways is a major site of remodeling in fatal asthma

Background Structural and inflammatory changes in asthma involve both the large and small airways, with involvement of the distal lung being related to disease severity. We have previously shown that changes in the extracellular matrix (ECM) composition of the distal lung are associated with loss of...

Full description

Saved in:
Bibliographic Details
Published in:Journal of allergy and clinical immunology 2009-05, Vol.123 (5), p.1090-1097.e1
Main Authors: Dolhnikoff, Marisa, MD, PhD, da Silva, Luiz F.F., MD, de Araujo, Bianca B., PhD, Gomes, Higor A.P., MD, Fernezlian, Sandra, MSc, Mulder, Adri, PhD, Lindeman, Jan H., MD, PhD, Mauad, Thais, MD, PhD
Format: Article
Language:English
Subjects:
Adult
Airway management
Allergy and Immunology
Asthma
Asthma - immunology
Asthma - metabolism
Asthma - pathology
Biological and medical sciences
Chronic obstructive pulmonary disease, asthma
Collagen
Collagen Type I - analysis
Collagen Type I - immunology
Collagen Type III - analysis
Collagen Type III - immunology
distal lung
extracellular matrix
Extracellular Matrix - immunology
Extracellular Matrix - metabolism
Extracellular Matrix - pathology
fatal asthma
Female
Fibronectins - analysis
Fibronectins - immunology
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humans
Immunopathology
Lung - immunology
Lung - metabolism
Lung - pathology
Male
Matrix Metalloproteinases - analysis
Matrix Metalloproteinases - immunology
Medical sciences
Middle Aged
Pathogenesis
Pneumology
Proteins
remodeling
Rodents
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
Software
Studies
Tissue Inhibitor of Metalloproteinases - analysis
Tissue Inhibitor of Metalloproteinases - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background Structural and inflammatory changes in asthma involve both the large and small airways, with involvement of the distal lung being related to disease severity. We have previously shown that changes in the extracellular matrix (ECM) composition of the distal lung are associated with loss of alveolar attachments in patients with fatal asthma. However, major ECM elements, such as collagen I and fibronectin and their regulators, have not been addressed at the distal level. Objective We sought to evaluate ECM remodeling in the distal lungs of asthmatic patients. Methods Using immunohistochemistry and image analysis, we determined the content of collagen I and III, fibronectin, and matrix metalloproteinases (MMPs) 1, 2, and 9 and tissue inhibitors of metalloproteinase (TIMPs) 1 and 2 in the large and small airways and lung parenchyma of 24 patients with fatal asthma and compared the results with those of 11 nonasthmatic control subjects. Protein content was defined as the area of positive staining divided by basement membrane or septum length. Results We observed increased collagen I and decreased collagen III content in the small airways of asthmatic patients compared with that seen in control subjects. Greater fibronectin and MMP-1, MMP-2, and MMP-9 content was observed at the outer area of the small airways in asthmatic patients. MMP content was also increased in the peribronchiolar parenchyma in asthmatic patients. In contrast, TIMP expression was only increased in the large airways of asthmatic patients compared with that seen in control subjects. Conclusions The outer area of the small airways is a major site of ECM remodeling in fatal asthma, potentially contributing to functional changes and the loss of airway-parenchyma interdependence observed in patients with fatal asthma.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2009.02.032