Miyagawa S, Shirakura R, Matsumiya G, Nakata S, Matsuda H, Hatanaka M, Matsumoto M, Kitamura H, Seya T
First Department of Surgery, Osaka University Medical School, Japan.
Scand J Immunol. 1993 Jul;38(1):37-44. doi: 10.1111/j.1365-3083.1993.tb01691.x.
We investigated the susceptibility to human complement (C) of xeno-erythrocytes into which phosphatidylinositol (PI)-anchored human C regulatory protein, decay-accelerating factor (DAF) or CD59 had been incorporated. Erythrocytes of sheep (Esh), swine (Esw), dog (Edg), and guinea pig (Egp), unsensitized with human natural antibody (Ab), were used as xeno-target. C-mediated lysis of erythrocytes (E) was induced in both classical and alternative pathways in parallel with the density of the sensitized Ab, except for Egp. The efficacy of DAF/CD59-mediated protection of the xeno E from human C, however, differed among these E species. In both classical and alternative pathways, Esh or Esw, which are non-activator surfaces, were protected by the incorporated DAF or CD59, DAF being more effective than CD59. On the other hand, CD59 was more effective than DAF in both pathways in protection of Egp, which is an alternative pathway activator. To elucidate this different behaviour of DAF and CD59, C3 step inhibition by the incorporated DAF or CD59 was measured. DAF was effective in the suppression of classical pathway-mediated C3 deposition in Esh, Esw and Egp, but not in Edg, while CD59 exhibited negligible effects in this regard. Next, inhibition of the lysis by CD59 was tested by haemolytic assay. CD59 did not block the C5b-8-mediated lysis in any xeno E. It also barely blocked C5b-9-mediated lysis, except in the case of Egp, in which CD59 partly blocked C9 attack. Membrane constituents on targets other than the incorporated complement inhibitors may be a crucial factor in the induction of cytolysis and, presumably, in hyperacute rejection.
我们研究了已掺入磷脂酰肌醇（PI）锚定的人补体（C）调节蛋白、衰变加速因子（DAF）或CD59的异种红细胞对人补体的敏感性。未被人天然抗体（Ab）致敏的绵羊（Esh）、猪（Esw）、狗（Edg）和豚鼠（Egp）的红细胞用作异种靶细胞。除Egp外，在经典途径和替代途径中，红细胞（E）的C介导裂解均与致敏Ab的密度平行诱导。然而，DAF/CD59介导的对异种E的人C保护作用在这些E物种中有所不同。在经典途径和替代途径中，作为非激活剂表面的Esh或Esw受到掺入的DAF或CD59的保护，DAF比CD59更有效。另一方面，在保护作为替代途径激活剂的Egp方面，CD59在两种途径中都比DAF更有效。为了阐明DAF和CD59的这种不同行为，测量了掺入的DAF或CD59对C3步骤的抑制作用。DAF可有效抑制经典途径介导的C3在Esh、Esw和Egp中的沉积，但对Edg无效，而CD59在这方面的作用可忽略不计。接下来，通过溶血试验测试CD59对裂解的抑制作用。CD59在任何异种E中均未阻断C5b-8介导的裂解。除了Egp的情况外，它也几乎未阻断C5b-9介导的裂解，在Egp中CD59部分阻断了C9攻击。除了掺入的补体抑制剂外，靶细胞上的膜成分可能是诱导细胞溶解以及可能是超急性排斥反应的关键因素。
