Interstitial collagen turnover during airway remodeling in acute and chronic experimental asthma.
Asthma airway remodeling is characterized by the thickening of the basement membrane (BM) due to an increase in extracellular matrix (ECM) deposition, which contributes to the irreversibility of airflow obstruction. Interstitial collagens are the primary ECM components to be increased during the fibrotic process. The aim of the present study was to examine the interstitial collagen turnover during the course of acute and chronic asthma, and 1 month after the last exposure to the allergen. Guinea pigs sensitized to ovalbumin (OVA) and exposed to 3 further OVA challenges (acute model) or 12 OVA challenges (chronic model) were used as asthma experimental models. A group of animals from either model was sacrificed 1 h or 1 month after the last OVA challenge. Collagen distribution, collagen content, interstitial collagenase activity and matrix metalloproteinase (MMP)-1, MMP-13 and tissue inhibitor of metalloproteinase (TIMP)-1 protein expression levels were measured in the lung tissue samples from both experimental models. The results revealed that collagen deposit in bronchiole BM, adventitial and airway smooth muscle layers was increased in both experimental models as well as lung tissue collagen concentration. These structural changes persisted 1 month after the last OVA challenge. In the acute model, a decrease in collagenase activity and in MMP-1 concentration was observed. Collagenase activity returned to basal levels, and an increase in MMP-1 and MMP-13 expression levels along with a decrease in TIMP-1 expression levels were observed in animals sacrificed 1 month after the last OVA challenge. In the chronic model, there were no changes in collagenase activity or in MMP-13 concentration, although MMP-1 expression levels increased. One month later, an increase in collagenase activity was observed, although MMP-1 and TIMP-1 levels were not altered. The results of the present study suggest that even when the allergen challenges were discontinued, and collagenase activity and MMP-1 expression increased, fibrosis remained, contributing to the irreversibility of bronchoconstriction.
Biomedical Oncology Laboratory, Department of Chronic-Degenerative Diseases, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', CP 14080 México City, Mexico.
Georgina
G
González-Avila
Department of Bronchial Hiperreactivity, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', CP 14080 México City, Mexico.
Blanca
B
Bazan-Perkins
Biomedical Oncology Laboratory, Department of Chronic-Degenerative Diseases, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', CP 14080 México City, Mexico.
Cuauhtémoc
C
Sandoval
Department of Bronchial Hiperreactivity, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', CP 14080 México City, Mexico.
Bettina
B
Sommer
Biomedical Oncology Laboratory, Department of Chronic-Degenerative Diseases, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', CP 14080 México City, Mexico.
Sebastian
S
Vadillo-Gonzalez
Department of Lung Fibrosis, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', CP 14080 México City, Mexico.
Carlos
C
Ramos
Biomedical Oncology Laboratory, Department of Chronic-Degenerative Diseases, National Institute of Respiratory Diseases 'Ismael Cosio Villegas', CP 14080 México City, Mexico.
Arnoldo
A
Aquino-Galvez
airway remodeling; asthma; collagen; collagenase activity; matrix metalloproteinase-1; matrix metalloproteinase-13; tissue inhibitor of metalloproteinase-1