Effects of azithromycin and tanomastat on experimental bronchiolitis obliterans Katharina Krenn, MD, Matthias Gmeiner, MD, PhD, Patrick Paulus, MD, Nezir.

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Presentation transcript:

Effects of azithromycin and tanomastat on experimental bronchiolitis obliterans Katharina Krenn, MD, Matthias Gmeiner, MD, PhD, Patrick Paulus, MD, Nezir Sela, MD, Linda Torres, MD, Karin Zins, PhD, Gerhard Dekan, MD, Seyedhossein Aharinejad, MD, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 149, Issue 4, Pages 1194-1202 (April 2015) DOI: 10.1016/j.jtcvs.2014.11.088 Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Macroscopic aspect of transplanted lungs. Macroscopic images of the posterior aspect of the lungs at 8 weeks posttransplant. The asterisk indicates the left transplanted lung. A, Isograft control; B, allograft control; C, AZI therapy; D, AZI+tano therapy. The Journal of Thoracic and Cardiovascular Surgery 2015 149, 1194-1202DOI: (10.1016/j.jtcvs.2014.11.088) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Histologic findings in transplanted lungs. Representative histologic images of lung allografts stained with HE for overview and EVG to stain collagen fibers. A, Allografts at 4 weeks following transplantation show dense leukocyte infiltration (asterisks), with only a small amount of collagen fibers (arrows in EVG images). B, Azithromycin group at 4 weeks after transplantation. C, At 8 weeks following transplantation, leukocyte infiltration (asterisks) is moderately decreased in control allografts, and increased deposition of collagen fibers is evident (arrows in EVG images). The azithromycin (D) and azithromycin+tanomastat groups (E) show less collagen deposition than the allograft controls (C). Original magnification ×100 in (A-E) to the left; field at higher magnification within the same slide (×400) to the right. HE, Hematoxylin-eosin; EVG, elastica van Gieson. The Journal of Thoracic and Cardiovascular Surgery 2015 149, 1194-1202DOI: (10.1016/j.jtcvs.2014.11.088) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Scoring of chronic vascular and chronic airway rejection in transplanted lungs. Relative frequencies of histologic categories for chronic vascular and chronic airway rejection in the allograft control and therapy groups. A, Relative frequencies of degrees of chronic vascular rejection. B, Relative frequencies of degrees of chronic airway rejection (severe means BO). Allo, Control allografts (n = 5 at 4 and 8 weeks); AZI, azithromycin treatment (n = 4 at 4 and 8 weeks); AZI+tano, azithromycin+tanomastat treatment (n = 4 at 8 weeks). The Journal of Thoracic and Cardiovascular Surgery 2015 149, 1194-1202DOI: (10.1016/j.jtcvs.2014.11.088) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Lung tissue protein expression of IL-12, IFN-γ, IL-17, MMP-9, and MMP-2. Results of Western blotting of protein extracted from whole lung tissue of the studied groups. Protein expression levels of IL-12 (A), IFN-γ (B), IL-17 (C), active and proMMP-9 (D and E) and MMP-2 (F), representative specific bands and loading controls are shown for each group. All data are presented as arbitrary units. *Indicates significantly different versus allografts at the same time point; #indicates significantly different versus isografts at the same time point. LC, Loading control; IL-12, interleukin-12; IFN-γ, interferon-γ; IL-17, interleukin-17; Iso, isograft; Allo, allograft; AZI, azithromycin treatment; AZI+tano, azithromycin+tanomastat treatment; MMP, matrix metalloprotease. The Journal of Thoracic and Cardiovascular Surgery 2015 149, 1194-1202DOI: (10.1016/j.jtcvs.2014.11.088) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 Immunofluorescent double-staining of IL-17 and CD8. A-D, Control allograft at 4 weeks: A, IL-17 (green); B, CD8 (red); C, DAPI nuclear staining (blue); D, merged image of IL-17, CD8, and DAPI. E-H, AZI-treated allograft at 4 weeks: E, IL-17 (green); F, CD8 (red); G, DAPI nuclear staining (blue); H, merged image of IL-17, CD8, and DAPI. White arrows indicate IL-17+/CD8+ double-stained cells, white bars in the lower right corner indicate 20 μm, original magnification ×400. The Journal of Thoracic and Cardiovascular Surgery 2015 149, 1194-1202DOI: (10.1016/j.jtcvs.2014.11.088) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions