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Respiratory Viral Infection in Obliterative Airway Disease After Orthotopic Tracheal Transplantation  Elbert Kuo, MD, Ankit Bharat, MD, Trudie Goers,

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Presentation on theme: "Respiratory Viral Infection in Obliterative Airway Disease After Orthotopic Tracheal Transplantation  Elbert Kuo, MD, Ankit Bharat, MD, Trudie Goers,"— Presentation transcript:

1 Respiratory Viral Infection in Obliterative Airway Disease After Orthotopic Tracheal Transplantation 
Elbert Kuo, MD, Ankit Bharat, MD, Trudie Goers, MD, Will Chapman, Le Yan, BS, Tyler Street, BA, Wei Lu, MD, Michael Walter, MD, Alexander Patterson, MD, Thalachallour Mohanakumar, PhD  The Annals of Thoracic Surgery  Volume 82, Issue 3, Pages (September 2006) DOI: /j.athoracsur Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

2 Fig 1 Orthotopic tracheal transplant model in which a 6-ring segment of trachea is transplanted and secured with three 10-0 nylon sutures at both ends. Sections for analysis were taken at approximately 100 μm, 250 μm, and 400 μm (4 μm thickness), represented by the yellow lines. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

3 Fig 2 (A) Using Image Pro Express v 4.0, percent fibrosis was calculated by dividing the area between the basement membrane and the cartilage by the total area enclosed by the tracheal cartilage. (B) The ratio of the lamina propria to cartilage thickness (LCR) was measured at 90, 180, and 270 degrees, with the membranous portion of the trachea positioned at the bottom of the section. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

4 Fig 3 Serial sections at 30 days after transplantation demonstrated incomplete reepithelialization with a multicellular matrix of squamous and ciliated cubiodal epithelium in the (A) allografts infected with a 5 K dose of Sendai virus (SdV) 15 days after transplantation. (B) As control, orthotopic isografts harvested at day 30 are presented. (F = fibrosis; I = infiltration.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

5 Fig 4 Allografts infected with 5 K Sendai virus (SdV) at 15 days had a significantly decreased (A) percent fibrosis and (B) thickness of lamina propria to cartilage ratio (LCR) compared with noninfected allografts. This decrease was not seen in isografts and nontransplanted controls infected with SdV. (White bars = no viral infection; black bars = 5 K SdV infection.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

6 Fig 5 (A) Allografts infected with Sendai virus (SdV) showed a dose-response decrease in percent fibrosis and thickness of lamina propria to cartilage ratio (LCR) at the 5 K and 25 K doses. Allografts infected with ultraviolet-inactivated, 1 K, and no virus showed no difference in fibrosis and LCR. (B) ELISPOT analysis showed parallel results with a dose-dependent decrease in the number of interferon-γ–producing cells as the SdV dose increased. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

7 Fig 6 Allografts infected with Sendai virus (SdV) 15 days after transplantation, showed an increase in (A) percent fibrosis and (B) thickness of lamina propria to cartilage ratio (LCR) at 60 days compared with at 30 days. (C) In addition, allografts infected with virus had increased frequency of interferon-γ–producing alloreactive T cells. (White bars = no viral infection; black bars = 5 K SdV infection.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

8 Fig 7 (A) Confirmation of sensitization of recipient mice with donor antigens (black) as evident by a shift in mean channel fluorescence compared with naïve recipients (red). Sera from sensitized recipients were reacted against donor splenocytes. Mice sensitized with donor antigens pretransplant showed no significant decrease in (B) percent fibrosis or (C) thickness of lamina propria to cartilage ratio (LCR) after Sendai virus (SdV) infection compared with nonsensitized allografts at day 30. (D) The number of interferon-γ–producing alloreactive T cells was not significantly decreased in sensitized mice after SdV infection on ELISPOT analysis. (White bars = no viral infection; black bars = 5 K SdV infection). The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

9 Fig 8 Mice previously infected with Sendai virus (SdV) did not show any reduction in (A) percent fibrosis and (B) thickness of lamina propria to cartilage ratio (LCR) at 30 days. At 60 days, mice previously infected with SdV showed significant reduction in tracheal allograft percent fibrosis, an opposite trend of allografts with no prior exposure. (White bars = 30 days after transplant; black bars = 60 days after transplant.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

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