Investigation Into The Effect Of HOPT And CsA On Acute Rejection In Tracheal Transplants In Mice

At present, the organ allograft rejection remains the most difficult problem faced in the field of organ transplantation. At the viewpoint of immune response, now that the trachea has merely one tissue-type, it is possible to induce short-term immune suppression on tracheal allotransplantation. Preliminary experimental studies have shown that 10-hydrocamptothecin (HOPT ) and cyclosporin A (CsA) had significantly immunosuppressive effect on acute rejection in heart and kidney allografts, thereby preserving structural and functional intact of transplanted organs, and reducing the side effect of immunosuppressants to recipient. However, because of the toxicity of high dose HOPT, we aim to explore if the combination of low dose of HOPT and CsA has synergic effect on the suppression on acute rejection of tracheal allografts in mice. In the present study, a heterotopic trachea transplant model in the mice was used with the combination of BALA/C donor and C57BL/6 recipient to study tracheal allograft rejection. Materials and MethodsAnimals: Thirty-two male BALA/C mice as donor and 32 male C57BL/6 mice as recipient were chosed for tracheal tranplantation.Methods and experimental protocol: Following euthanasia of the donor, the tracheas were taken out and placed in abdominal cavity whereby wrapping with omentopexy of the recipients under sterile condition. The animals underwent immunosuppressive treatment with HOPT alone, CsA along, and the combination of HOPT and CsA postoperatively. Thus, the animals were randomly divided into 4 group according to the difference in postoperative treatment, including group A (n=8): lavage no immunosuppressants; group B (n=8):peritoneal injection of HOPT (0.015mg/d); group C (n=8): oral addition of CsA (0.3mg/d) via gastric lavage; group D (n=8): peritoneal injection of HOPT (0.015mg/d) and oral addition of CsA (0.3mg/d) via gastric lavage. The animals were killed 4 weeks after transplantation, and the tracheal grafts were taken out for pathology study.ResultsIn the group A, B, C, and group D, tracheal swelling and severe stenosis of the tracheal lumen were present. Under microscope, in group A, mucosal desquamation, cartilage necrosis, fresh granulation tissue proliferation, and lymphocyte and monocyte proliferation. Of the proliferation monocytes were mainly present around the submucosal and extramucosal vessels or the lumen of thrombosed vasculatures of tracheal grafts. In the Bgroup,the tracheal grafts are presented as partialmucosal desquamation, cartilage degradation, severe fresh granulation tissue proliferation, and moderate lymphocyte and monocyte proliferation, whereas proliferating monocytes are mainly were present around the submucosal and extramucosal vessels or the lumen of thrombosed vasculatures of tracheal grafts. In group C, the tracheal grafts are presented as partial mucosal desquamation, cartilage degradation, mild fresh granulation tissue proliferation, and mild lymphocyte and monocyte proliferation, whereas proliferating monocytes were mainly present around the submucosal and extramucosal vessels or the lumen of thrombosed vasculatures of tracheal grafts. In group D, the tracheal grafts are presented as partial mucosal desquamation, lack of cartilage degradation, necrosis and dissolution and absorption, mild fresh granulation tissue proliferation, and mild lymphocyte and monocyteproliferation, whereas proliferating monocytes were also mainly present around the submucosal and extramucosal vessels or the lumen of thrombosed vasculatures of tracheal grafts. In comparison with group A, the degree of mucosal desquamation, cartilage degradation, necrosis or dissolution and absorption, fresh granulation tissue proliferation, and lymphocyte and monocyte infiltration was decreased in group A. In group C, the degree of mucosal disputation, cartilage degradation, necrosis or dissolution and absorption, fresh granulation tissue proliferation, and lymphocyte and monocyte infiltration was significantly lessened co...