Brandt Michael, Grotkop Christian, Steinmann Jörg, Steinhoff Gustav
Department of Cardiovascular Surgery, University-Hospital, Arnold-Heller-Strasse 7, 24105 Kiel, Germany.
Interact Cardiovasc Thorac Surg. 2003 Dec;2(4):509-13. doi: 10.1016/S1569-9293(03)00131-2.
Infiltration of leukocytes into the lung allograft is regulated by adhesion molecules during acute rejection. The purpose of this study was to assess the effect of monoclonal antibodies against ICAM-1 (1A29) to prevent rejection after lung transplantation. Left lateral orthotopic lung transplantation was performed using Dark Agouti rats as donors and Lewis rats as recipients. Recipients received 1A29 alone (group A), cyclosporine A alone (group B), a combination of both drugs (group C) or no therapy (group D). Animals were killed on day 5 and 10, respectively. Rejection was graded by histology. Myeloperoxidase activity (MPO) was measured in the graft. In allografts treated with cyclosporine and 1A29 histologically a lower grade of rejection was seen and less MPO were detected compared to groups A, B and D. Anti-ICAM-1 monoclonal antibodies alone as well as a subtherapeutic dose of cyclosporine are not effective to prevent acute allograft rejection after lung transplantation. However, the combination of both strategies significantly reduces rejection in this model.
在急性排斥反应期间,白细胞向同种异体肺移植组织的浸润受黏附分子调控。本研究的目的是评估抗细胞间黏附分子-1单克隆抗体(1A29)预防肺移植后排斥反应的效果。采用深褐大鼠作为供体、刘易斯大鼠作为受体进行左外侧原位肺移植。受体分别接受单独的1A29(A组)、单独的环孢素A(B组)、两种药物联合使用(C组)或不进行治疗(D组)。分别在第5天和第10天处死动物。通过组织学对排斥反应进行分级。测定移植组织中的髓过氧化物酶活性(MPO)。与A组、B组和D组相比,在接受环孢素和1A29治疗的同种异体移植组织中,组织学上观察到的排斥反应等级较低,且检测到的MPO较少。单独使用抗ICAM-1单克隆抗体以及低于治疗剂量的环孢素对预防肺移植后的急性同种异体移植排斥反应均无效。然而,在该模型中,两种策略联合使用可显著降低排斥反应。