Xu H, Kwiatkowski P, Chen J M, Kaplon R J, Edwards N M, Dong X, Berger C, Michler R E
Cardiac Transplantation Research Laboratory, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Transplantation. 1994 Dec 27;58(12):1299-303.
Natural xenoantibodies are believed to be IgM in nature and are known to play a critical role in the hyperacute rejection of distantly related xenografts. The purpose of this study was to determine whether the reducing agent DL-penicillamine could inactivate baboon natural xenoantibodies to pig splenocytes. Pooled baboon serum was treated with varying concentrations of DL-penicillamine over different lengths of time and a complement-mediated cytotoxicity assay was used to determine the reactivity of baboon natural xenoantibodies to pig splenocytes. A whole-cell ELISA assay was used to assess the binding of both IgG and IgM xenoantibodies to pig splenocytes. In addition, DL-penicillamine-treated serum was dialyzed to assess its potential clinical application. These in vitro experiments indicate that both IgM and IgG baboon natural xenoantibodies bind to pig splenocytes, but only IgM xenoantibody is cytotoxic. The binding of baboon natural IgM xenoantibody can be eliminated, and the cytotoxicity of IgM xenoantibody markedly reduced by DL-penicillamine treatment despite continued binding of IgG xenoantibody to pig splenocytes. In addition, DL-penicillamine can be dialyzed, suggesting that it may be an efficacious clinical treatment, the toxicity of which can be regulated with hemodialysis.
天然异种抗体在本质上被认为是IgM，并且已知在远缘异种移植物的超急性排斥反应中起关键作用。本研究的目的是确定还原剂DL-青霉胺是否能使狒狒针对猪脾细胞的天然异种抗体失活。将混合的狒狒血清用不同浓度的DL-青霉胺处理不同时长，并用补体介导的细胞毒性试验来确定狒狒天然异种抗体对猪脾细胞的反应性。使用全细胞ELISA试验来评估IgG和IgM异种抗体与猪脾细胞的结合情况。此外，对经DL-青霉胺处理的血清进行透析以评估其潜在的临床应用。这些体外实验表明，狒狒的IgM和IgG天然异种抗体均能与猪脾细胞结合，但只有IgM异种抗体具有细胞毒性。通过DL-青霉胺处理，狒狒天然IgM异种抗体的结合可以被消除，尽管IgG异种抗体仍继续与猪脾细胞结合，但IgM异种抗体的细胞毒性会显著降低。此外，DL-青霉胺可以被透析，这表明它可能是一种有效的临床治疗方法，其毒性可以通过血液透析来调节。
