Fiane A E, Videm V, Johansen H T, Mellbye O J, Nielsen E W, Mollnes T E
Department of Surgery A, University of Oslo, The National Hospital, Norway.
Immunopharmacology. 1999 May;42(1-3):231-43. doi: 10.1016/s0162-3109(99)00008-9.
Xenotransplantation may be a future alternative due to increased shortage of organs. Classical complement activation is central in hyperacute rejection in pig-to-human combinations. We investigated the effects of C1-inhibitor (C1-INH), a regulator of the complement and contact systems, on hyperacute rejection. Pig kidneys were perfused with fresh human blood to which either C1-INH (n = 6) or human serum albumin (n = 6) was added. The survival of the C1-INH perfused kidneys (mean 327 min) was significantly longer (p < 0.00001) than the controls (79 min). C1-INH substantially inhibited complement activation (C1rs-C1-INH complexes, C4bc, C3bc and terminal complement complex) (p < 0.001 for all) compared with the marked complement activation in the controls. No contact activation was found. Leukocytes and platelets were substantially activated (counts, myeloperoxidase, beta-thromboglobulin, thrombospondin, soluble P-selectin) in the control group, and this activation was markedly reduced by C1-INH (p < 0.02 for all). Immunohistochemistry showed less C1q, C3, TCC, IgG and fibrin deposition in the C1-INH group. C1-INH may be useful to attenuate hyperacute rejection, probably through inhibition of complement. The reduced activation of neutrophils and platelets may mainly be secondary to inhibition of complement.
由于器官短缺日益严重，异种移植可能成为未来的一种选择。经典补体激活在猪到人的超急性排斥反应中起核心作用。我们研究了补体和接触系统的调节剂C1抑制剂（C1-INH）对超急性排斥反应的影响。用添加了C1-INH（n = 6）或人血清白蛋白（n = 6）的新鲜人血灌注猪肾。灌注C1-INH的肾脏的存活时间（平均327分钟）明显长于对照组（79分钟）（p < 0.00001）。与对照组明显的补体激活相比，C1-INH显著抑制补体激活（C1rs-C1-INH复合物、C4bc、C3bc和末端补体复合物）（所有p < 0.001）。未发现接触激活。对照组中白细胞和血小板大量激活（计数、髓过氧化物酶、β-血小板球蛋白、血小板反应蛋白、可溶性P-选择素），而C1-INH显著降低了这种激活（所有p < 0.02）。免疫组织化学显示C1-INH组中C1q、C3、TCC、IgG和纤维蛋白沉积较少。C1-INH可能有助于减轻超急性排斥反应，可能是通过抑制补体。中性粒细胞和血小板激活的减少可能主要是补体抑制的继发效应。
