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Published ahead of print on January 26, 2006, doi:10.1165/rcmb.2006-0002OC

Am. J. Respir. Cell Mol. Biol., Volume 34, Number 6, June 2006, 688-694

A more recent version of this article appeared on June 1, 2006
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Submitted on November 10, 2005
Revised on January 26, 2006

Early Emphysema in the Tight Skin and the Pallid Mice: Roles of Microfibril Associated Glycoproteins, Collagen and Mechanical Forces

Satoru Ito1, Erzsebet Bartolak-Suki2, J. Michael Shipley3, Harikrishnan Parameswaran1, Arnab Majumdar1, and Bela Suki1*

1 Department of Biomedical Engineering, Boston University, Boston, MA, USA, 2 Aeris Therapeutics, Inc., Woburn, MA, USA, 3 Washington University School of Medicine, St. Louis, MO, USA

* To whom correspondence should be addressed. E-mail: bsuki{at}bu.edu.

Rationale: The nature of the development of emphysema in the tight skin (Tsk) and the pallid (Pa) mice are not well understood. Methods: We assessed the mechanical and nonlinear properties of the respiratory system, the alveolar structure, and the levels of microfibril associated glycoproteins (MAGP) 1 and 2 in Tsk mice with developmental emphysema, in Pa mice, which are known to develop adult onset emphysema, and their background, the C57BL/6 mice, at an age of 7 weeks. Results: Minor differences between collagen-related elastic properties of the lungs of the Pa and C57BL/6 mice were seen at this early age. The lungs of the Tsk mice were significantly softer yet more nonlinear than those of the Pa and C57BL/6 mice. The MAGP-1 levels were similar in all three groups. However, the level of MAGP-2, which is associated with both fibrillin-1 and collagen, was higher in the Tsk mice than in the Pa, which also had more MAGP-2 than the C57BL/6. Both the mean and the variance of alveolar diameters were larger in the Tsk than in the other two groups while the variance in the Pa was larger than in the C57BL/6 mice implying early development of heterogeneity. Using a network model of the parenchyma, we linked the pathophysiological changes in the Tsk mice to mechanical forces and failure of the alveolar walls. Conclusion: Our findings suggest the possibility that MAGP-2 related abnormal collagen assembly combined with mechanical forces is involved in the progression of emphysema in the Tsk mice.




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