Stress responses in graft and native intestine after rat heterotopic small bowel transplantation.

Abstract

Cardiac transplantation has been shown to induce heat shock protein expression, and reactivity to these stress proteins has been implicated in acute and chronic allograft rejection. This study assessed Hsp60 and Hsp70 expression in graft and native small intestine after rat small bowel transplantation. Heterotopic small bowel transplantation was performed between PVG donor and DA recipient rats, a subgroup of which received tacrolimus immunosuppression (1 mg x kg(-1) x day(-1)). Untransplanted and isografted (PVG-->PVG) animals served as controls. Paraffin sections of graft and native intestine on day 5 after transplantation were stained by immunohistochemistry, and heat shock protein expression was graded blindly by three observers. Villus epithelial cell expression of Hsp60, but not Hsp70, was increased in allografts. The induction of Hsp60 in the villus epithelium was not controlled by tacrolimus. Hsp60 and Hsp70 expression was induced in the lamina propria of isografts and allografts. This response was more pronounced in allografts and was significantly reduced, but not totally abrogated, by tacrolimus. Interestingly, heat shock protein expression was also induced in the native intestine lamina propria and epithelium of allograft recipients, suggesting the induction of stress responses at sites other than the transplanted organ. Small bowel transplantation induces a stress response in both the graft and native intestine. The early and prolonged expression of these proteins may influence the induction of anti-heat shock protein reactivity and have an adverse effect on graft outcome after small bowel transplantation.