Limits...
Interstitial collagen turnover during airway remodeling in acute and chronic experimental asthma

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Guinea pig bronchiole histopathological features. Collagen fibers were increased in the bronchiole adventitial layer (red arrows), in the airway smooth muscle layer (blue arrows), and in the basement membranes (green arrows) in the tissue samples from guinea pigs of the 35 day experimental model sacrificed 1 h after hyperresponsiveness determination (group II). The increase in collagen fibers was more evident in bronchioles from the 125 day model (group II). Epithelial hyperplasia was also observed in bronchioles in the guinea pigs of this group. The increase in collagen deposition remained in the bronchioles 1 month after the last ovalbumin challenge (group III). Original magnification, ×40.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4998200&req=5

f4-etm-0-0-3509: Guinea pig bronchiole histopathological features. Collagen fibers were increased in the bronchiole adventitial layer (red arrows), in the airway smooth muscle layer (blue arrows), and in the basement membranes (green arrows) in the tissue samples from guinea pigs of the 35 day experimental model sacrificed 1 h after hyperresponsiveness determination (group II). The increase in collagen fibers was more evident in bronchioles from the 125 day model (group II). Epithelial hyperplasia was also observed in bronchioles in the guinea pigs of this group. The increase in collagen deposition remained in the bronchioles 1 month after the last ovalbumin challenge (group III). Original magnification, ×40.

Mentions: Masson's trichrome stain revealed an increase in collagen deposit (blue stain) in bronchiole BM (green arrows) and in the adventitial layers (red arrows) in guinea pigs from both experimental models (groups II; Fig. 4). Blue bands were also observed in and around airway smooth muscle (ASM) layers (blue arrows). The increase in connective tissue deposit was more evident in group II from the 125 days model. The increase in collagen deposit remained despite cessation of the antigen exposition in both models. Epithelial hyperplasia was observed in bronchioles from both experimental models although it was more evident in animals from the 125 days model. The bronchiole epithelial hyperplasia decreased when OVA challenges ceased in the 125 days model (group III), although it persisted in both experimental models 1 month after the last OVA challenge.


Interstitial collagen turnover during airway remodeling in acute and chronic experimental asthma
Guinea pig bronchiole histopathological features. Collagen fibers were increased in the bronchiole adventitial layer (red arrows), in the airway smooth muscle layer (blue arrows), and in the basement membranes (green arrows) in the tissue samples from guinea pigs of the 35 day experimental model sacrificed 1 h after hyperresponsiveness determination (group II). The increase in collagen fibers was more evident in bronchioles from the 125 day model (group II). Epithelial hyperplasia was also observed in bronchioles in the guinea pigs of this group. The increase in collagen deposition remained in the bronchioles 1 month after the last ovalbumin challenge (group III). Original magnification, ×40.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998200&req=5

f4-etm-0-0-3509: Guinea pig bronchiole histopathological features. Collagen fibers were increased in the bronchiole adventitial layer (red arrows), in the airway smooth muscle layer (blue arrows), and in the basement membranes (green arrows) in the tissue samples from guinea pigs of the 35 day experimental model sacrificed 1 h after hyperresponsiveness determination (group II). The increase in collagen fibers was more evident in bronchioles from the 125 day model (group II). Epithelial hyperplasia was also observed in bronchioles in the guinea pigs of this group. The increase in collagen deposition remained in the bronchioles 1 month after the last ovalbumin challenge (group III). Original magnification, ×40.
Mentions: Masson's trichrome stain revealed an increase in collagen deposit (blue stain) in bronchiole BM (green arrows) and in the adventitial layers (red arrows) in guinea pigs from both experimental models (groups II; Fig. 4). Blue bands were also observed in and around airway smooth muscle (ASM) layers (blue arrows). The increase in connective tissue deposit was more evident in group II from the 125 days model. The increase in collagen deposit remained despite cessation of the antigen exposition in both models. Epithelial hyperplasia was observed in bronchioles from both experimental models although it was more evident in animals from the 125 days model. The bronchiole epithelial hyperplasia decreased when OVA challenges ceased in the 125 days model (group III), although it persisted in both experimental models 1 month after the last OVA challenge.

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus