A rat small bowel transplant model of chronic rejection: Histopathologic characteristics

Susan Orloff, Qiang (Michael) Yin, Christopher Corless, Christopher B. Loomis, John M. Rabkin, Cynthia R. Wagner

Research output: Contribution to journalArticle

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Abstract

Background. The major impediment to long-term success in solid organ transplantation is the development of chronic rejection (CR). The vascular lesion of CR, transplant vascular sclerosis (TVS) is characterized by neointimal smooth muscle cell proliferation, and is driven by both immune- and nonimmune-mediated mechanisms. Although the features of chronic heart and kidney allograft rejection have been well characterized, the more immunogenic small bowel allograft has not received similar study. Methods. F344 small bowel (SB) was transplanted heterotopically into Lewis recipients that were treated with low-dose Cyclosporine A for 15 days. Lewis recipients of F344 or Lewis SB grafts without immunosuppression, served as controls. Grafts were assessed histologically when recipients showed clinical signs of rejection or at predetermined time points. The immunological components involved in the chronic rejection process were evaluated by immunohistochemical staining. Results. All SB allografts (100%) developed histologic evidence of CR Cyclosporine A. TVS was seen in 36 of the 46 (78%) of these allografts. The median time to develop TVS was 45 days. Immunohistochemical staining of chronically rejected grafts showed infiltration predominantly by CD4+ cells and macrophages, uniform up-regulation of class II MHC molecule expression, moderate to intense ICAM-1 staining in grafts harvested at postoperative day 45, and uniform neointimal cell staining for smooth muscle cell α-actin in the TVS lesions. Conclusions. This F344 to Lewis SB transplant model is a useful model that reproduces significant features of CR. The highly immunogenic nature of the SB allografts allows this model to serve as a stringent test for protocols designed to prevent CR.

Original languageEnglish (US)
Pages (from-to)766-779
Number of pages14
JournalTransplantation
Volume68
Issue number6
DOIs
StatePublished - Sep 27 1999

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Transplants
Arteriosclerosis
Allografts
Staining and Labeling
Cyclosporine
Smooth Muscle Myocytes
Graft Rejection
Organ Transplantation
Intercellular Adhesion Molecule-1
Immunosuppression
Blood Vessels
Actins
Up-Regulation
Macrophages
Cell Proliferation
Kidney

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

A rat small bowel transplant model of chronic rejection : Histopathologic characteristics. / Orloff, Susan; Yin, Qiang (Michael); Corless, Christopher; Loomis, Christopher B.; Rabkin, John M.; Wagner, Cynthia R.

In: Transplantation, Vol. 68, No. 6, 27.09.1999, p. 766-779.

Research output: Contribution to journalArticle

Orloff, Susan ; Yin, Qiang (Michael) ; Corless, Christopher ; Loomis, Christopher B. ; Rabkin, John M. ; Wagner, Cynthia R. / A rat small bowel transplant model of chronic rejection : Histopathologic characteristics. In: Transplantation. 1999 ; Vol. 68, No. 6. pp. 766-779.
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N2 - Background. The major impediment to long-term success in solid organ transplantation is the development of chronic rejection (CR). The vascular lesion of CR, transplant vascular sclerosis (TVS) is characterized by neointimal smooth muscle cell proliferation, and is driven by both immune- and nonimmune-mediated mechanisms. Although the features of chronic heart and kidney allograft rejection have been well characterized, the more immunogenic small bowel allograft has not received similar study. Methods. F344 small bowel (SB) was transplanted heterotopically into Lewis recipients that were treated with low-dose Cyclosporine A for 15 days. Lewis recipients of F344 or Lewis SB grafts without immunosuppression, served as controls. Grafts were assessed histologically when recipients showed clinical signs of rejection or at predetermined time points. The immunological components involved in the chronic rejection process were evaluated by immunohistochemical staining. Results. All SB allografts (100%) developed histologic evidence of CR Cyclosporine A. TVS was seen in 36 of the 46 (78%) of these allografts. The median time to develop TVS was 45 days. Immunohistochemical staining of chronically rejected grafts showed infiltration predominantly by CD4+ cells and macrophages, uniform up-regulation of class II MHC molecule expression, moderate to intense ICAM-1 staining in grafts harvested at postoperative day 45, and uniform neointimal cell staining for smooth muscle cell α-actin in the TVS lesions. Conclusions. This F344 to Lewis SB transplant model is a useful model that reproduces significant features of CR. The highly immunogenic nature of the SB allografts allows this model to serve as a stringent test for protocols designed to prevent CR.

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