Naka Y, Marsh H C, Scesney S M, Oz M C, Pinsky D J
Department of Physiology, Columbia University, New York, New York 10032, USA.
Transplantation. 1997 Nov 15;64(9):1248-55. doi: 10.1097/00007890-199711150-00004.
Although agents that inhibit complement activation may be beneficial in discordant xenotransplantation, it is not known whether local complement activation occurs and is deleterious after isogeneic lung transplantation. Lungs were harvested from Lewis rats subjected to 4 degrees C 6-hr preservation followed by transplantation into strain-, gender-, and weight-matched recipients. Transplanted lungs demonstrated increased immunostaining for C5b-9 compared with nontransplanted controls, confirming local complement activation in this isograft model. To investigate the physiologic relevance of complement activation in the transplanted lung, the native pulmonary artery was ligated after transplantation, and pulmonary vascular resistance (mmHg/ml/min), arterial oxygenation (mmHg), graft neutrophil infiltration (myeloperoxidase activity, deltaAbs 460 nm/min), and recipient survival were measured at 30 min. Animals received either saline (control; n=22) or soluble complement receptor type-1 (sCR1, 15 mg/kg; n=19) 2 min before reperfusion. Animals treated with sCR1 showed a marked reduction in serum complement hemolytic activity (CH50; 90% lower than that of control animals, P<0.001). Compared with controls, sCR1-treated animals showed reduced pulmonary vascular resistance (2.9+/-1.1 vs. 8.5+/-1.5 mmHg/ml/min, P<0.05), improved arterial oxygenation (194+/-34 vs. 91+/-17 mmHg, P<0.05), decreased neutrophil infiltration (35% decrease, P<0.005), and improved recipient survival (74% vs. 23%, P<0.005). In parallel with the reduction in complement hemolytic activity in sCR1-treated animals, immunohistology of the transplanted lung revealed decreased C5b-9 deposition compared with controls. Taken together, these data indicate that complement activation occurs after lung preservation and transplantation in an isograft model, and that inhibiting complement activation improves outcome after transplantation.
尽管抑制补体激活的药物可能对异种移植有益，但同种基因肺移植后局部补体激活是否发生及其是否有害尚不清楚。从Lewis大鼠获取肺脏，经4℃保存6小时后移植到品系、性别和体重匹配的受体中。与未移植的对照组相比，移植肺的C5b - 9免疫染色增加，证实了该同基因移植模型中存在局部补体激活。为了研究移植肺中补体激活的生理相关性，移植后结扎天然肺动脉，并在30分钟时测量肺血管阻力（mmHg/ml/min）、动脉氧合（mmHg）、移植肺中性粒细胞浸润（髓过氧化物酶活性，ΔAbs 460 nm/min）和受体存活率。在再灌注前2分钟，动物分别接受生理盐水（对照组；n = 22）或可溶性补体受体1（sCR1，15 mg/kg；n = 19）。接受sCR1治疗的动物血清补体溶血活性（CH50）显著降低（比对照动物低90%，P < 0.001）。与对照组相比，接受sCR1治疗的动物肺血管阻力降低（2.9±1.1 vs. 8.5±1.5 mmHg/ml/min，P < 0.05），动脉氧合改善（194±34 vs. 91±17 mmHg，P < 0.05），中性粒细胞浸润减少（降低35%，P < 0.005），受体存活率提高（74% vs. 23%，P < 0.005）。与接受sCR1治疗的动物补体溶血活性降低相一致，移植肺的免疫组织学显示与对照组相比C5b - 9沉积减少。综上所述，这些数据表明在同基因移植模型中，肺保存和移植后会发生补体激活，并且抑制补体激活可改善移植后的结果。
