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Published ahead of print on August 2, 2007, doi:10.1165/rcmb.2007-0249OC

Am. J. Respir. Cell Mol. Biol., Volume 38, Number 1, January 2008, 16-25

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Submitted on June 29, 2007
Revised on August 2, 2007

Decreased Asbestos-Induced Lung Inflammation and Fibrosis after Radiation and Bone Marrow Transplant

Jamie Levis1, Roberto Loi2, Kelly J Butnor1, Pamela Vacek3, Chad Steele4, Brooke T Mossman1, and Daniel J Weiss2*

1 Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA, 2 Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA, 3 Department of Biostatistics, University of Vermont College of Medicine, Burlington, Vermont, USA, 4 Department of Pediatrics, University of Pittsburgh College of Medicine, Pittsburgh, Pennsylvania, USA

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

Rationale: The effect of lung irradiation on subsequent inflammatory or fibrotic lung injuries remains poorly understood. We postulated that irradiation and bone marrow transplantation might impact the development and progression of lung remodeling resulting from asbestos inhalation. Objective: To determine whether irradiation and bone marrow transplantation affected inflammation and fibrosis associated with inhaled asbestos exposure. Methods: Inflammation, cytokine production, and fibrosis were assessed in lungs of naive and sex-mismatched chimeric mice exposed to asbestos for 3, 9, or 40 days. Potential engraftment of donor-derived cells in recipient lungs was examined by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Measurements and Main Results: In comparison to asbestos-exposed naive (non-chimeric) mice, chimeric mice exposed to asbestos for 3, 9, or 40 days demonstrated significant abrogation of acute increases in asbestos-associated inflammatory mediators and fibrosis. Donor-derived cells trafficked to lung but did not significantly engraft as phenotypic lung cells. Conclusions: Irradiation and bone marrow transplantation alters inflammatory and fibrotic responses to asbestos, likely through modulation of soluble inflammatory mediators.




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