Immunoregulation Effect by Overexpression of Heme Oxygenase-1 on Cardiac Xenotransplantation

Objective. This study was designed to investigate the effect of the overexpression of heme oxygenase-1 (HO-1) on the immunoregulation in the model of abdominal cardiac xenotransplantation from the guinea pig to the rat. Materials and methods. To increase the expression of HO-1, both donors and recipients were injected with heme through the abdomen before the operation. The donors (guniea pigs) and the recipients (Sprague-Dawley [SD] rats) were divided randomly into three groups: group A, the heart from a guinea pig transplanted into the abdomen of an SD rat; group B, the recipients were injected with Chinese cobra venom factor (CVF) into the abdomen (40 mu g/kg and 60 mu g/kg 24 hours later) prior to transplantation; group C, CVF + HO-1 high-expression group: donors and recipients were abdominally injected with heme (75 mu mol/kg for 2 days before transplantation). The mean survival time (MST), pathological changes, the positive area of HO-1 in the grafted hearts, as well as the expressions of C-C chemokine receptor 5 (CCR5), intercellular adhesion molecule-1 (ICAM-1), and natural killer (NK) cell activity in recipients. Results. 1. The MST was longest in group C treated with heme. 2. The pathologic changes of hyperacute rejection were showed on the donor heart in group A, while delayed xenograft rejection changes took place on donor heart in other groups. 3. Compared with group B, The HO-1 positive area in the donor hearts of group C was significantly higher. (P < .05). 4. The lever of ICAM-1 and CCR5 in the peripheral blood of recipients (pg/mL) was attenuated in group C injected with heme. 5. Compared with group B, the activity of NK cell in the peripheral blood of recipients was much lower in group C (P < .05). Conclusion. The MST was prolonged by increasing expressions of HO-1, but acute vascular rejection was not completely overcome. Activation of vascular endothelial cells could be decreased by strengthening the expression of HO-1. NK cell activity was weakened by reinforced expression of HO-1.