Rapamycin Blocks Fibrocyte Migration and Attenuates Bronchiolitis Obliterans in a Murine Model Jacob R. Gillen, MD, Yunge Zhao, MD, PhD, David A. Harris,

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Rapamycin Blocks Fibrocyte Migration and Attenuates Bronchiolitis Obliterans in a Murine Model Jacob R. Gillen, MD, Yunge Zhao, MD, PhD, David A. Harris, BS, Damien J. LaPar, MD, Matthew L. Stone, MD, Lucas G. Fernandez, MD, Irving L. Kron, MD, Christine L. Lau, MD, MBA The Annals of Thoracic Surgery Volume 95, Issue 5, Pages 1768-1775 (May 2013) DOI: 10.1016/j.athoracsur.2013.02.021 Copyright © 2013 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Representative immunohistochemical staining of tracheal grafts for smooth muscle actin (SMA) at day 14 after transplantation. Dimethyl sulfoxide (DMSO) controls demonstrate positive SMA staining (Fast-Red) within the tracheal lumen, indicative of the developing fibrosis. Rapamycin-treated tracheas show no SMA staining within the lumen. (Magnification, ×40. BF = bright field; Fast-Red = SMA stain; DAPI = 4',6-diamidino-2-phenylindole [nuclear stain; Merged = Fast-Red + DAPI together.) The Annals of Thoracic Surgery 2013 95, 1768-1775DOI: (10.1016/j.athoracsur.2013.02.021) Copyright © 2013 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 Rapamycin treatment reduces luminal obliteration of tracheal allografts at day 28 after transplantation. (A) Images of representative hematoxylin and eosin stains of tracheal allografts. Dimethyl sulfoxide (DMSO)-treated specimens show complete luminal obliteration with fibrosis; rapamycin-treated specimens shows no luminal obliteration (pink substance within lumen is mucus). (B) Bar graph of percent luminal obliteration in each treatment group; n = 8 tracheas per group. Data shown are mean ± standard error of the mean. The Annals of Thoracic Surgery 2013 95, 1768-1775DOI: (10.1016/j.athoracsur.2013.02.021) Copyright © 2013 The Society of Thoracic Surgeons Terms and Conditions