Roles of Mechanical Forces and Collagen Failure in the Development of Elastase-induced Emphysema

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Abstract
Emphysema causes a permanent destruction of alveolar walls leading to airspace enlargement, loss of elastic recoil, decrease in surface area for gas exchange, lung hyperexpansion, and increased work of breathing. The most accepted hypothesis of how emphysema develops is based on an imbalance of protease and antiprotease activity leading to the degradation of elastin within the fiber network of the extracellular matrix. Here we report novel roles for mechanical forces and collagen during the remodeling of lung tissue in a rat model of elastase-induced emphysema. We have developed a technique to measure the stress-strain properties of tissue sections while simultaneously visualizing the deformation of the immunofluorescently labeled elastin-collagen network. We found that in the elastase treated tissue significant remodeling leads to thickened elastin and collagen fibers and during stretching, the newly deposited elastin and collagen fibers undergo substantially larger distortions than in normal tissue. We also found that the threshold for mechanical failure of collagen, which provides mechanical stability to the normal lung, is reduced. Our results indicate that mechanical forces during breathing are capable of causing failure of the remodeled extracellular matrix at loci of stress concentrations and so contribute to the progression of emphysema.