Xu H, Edwards N, Chen J M, Dong X, Michler R E
Cardiac Transplantation Research Laboratory, Columbia Presbyterian Medical Center, New York, N.Y. 10032, USA.
J Thorac Cardiovasc Surg. 1995 Oct;110(4 Pt 1):1023-9. doi: 10.1016/s0022-5223(05)80170-9.
Human cytotoxic natural xenoantibodies are believed to be of the immunoglobulin M class in nature. However, a thorough understanding of the development of these natural antixenodonor xenoantibodies remains incomplete. In this study, serum samples were obtained from newborn, infant, and adult human beings. An enzyme-linked immunosorbent assay was used to determine the binding of human natural immunoglobulin M xenoantibodies to pig aortic endothelial cells and pig lymphocytes. A complement-mediated cytotoxicity assay was used to measure the cytotoxicity of newborn, infant, and adult serum to cultured pig aortic endothelial cells and pig lymphocytes. Adult human serum contained both natural immunoglobulin M and immunoglobulin G xenoantibodies to pig endothelial cells and lymphocytes, whereas newborn infant serum contained only immunoglobulin G xenoantibodies. Only adult human serum was cytotoxic to pig endothelial cells and lymphocytes. Human immunoglobulin M xenoantibodies became detectable by age 1 month. By age 2 months these natural anti-pig xenoantibodies reached serum levels equivalent to those in the human adult and resulted in similar cytotoxicity to that of adult human serum. These findings indicate that (1) natural anti-pig immunoglobulin M xenoantibodies are absent from newborn infant human serum, (2) newborn human serum is not cytotoxic to pig endothelial cells and lymphocytes despite the presence of immunoglobulin G xenoantibodies that bind to pig endothelial cells and lymphocytes, and (3) natural anti-pig immunoglobulin M xenoantibodies begin to develop as early as age 1 month and by age 2 months attain a circulating level comparable to that found in the adult.
人们认为人类细胞毒性天然异种抗体本质上属于免疫球蛋白M类。然而，对这些天然抗异种供体异种抗体的产生过程仍缺乏全面了解。在本研究中，采集了新生儿、婴儿和成人的血清样本。采用酶联免疫吸附测定法来确定人类天然免疫球蛋白M异种抗体与猪主动脉内皮细胞和猪淋巴细胞的结合情况。采用补体介导的细胞毒性测定法来检测新生儿、婴儿和成人血清对培养的猪主动脉内皮细胞和猪淋巴细胞的细胞毒性。成人血清中含有针对猪内皮细胞和淋巴细胞的天然免疫球蛋白M和免疫球蛋白G异种抗体，而新生儿血清中仅含有免疫球蛋白G异种抗体。只有成人血清对猪内皮细胞和淋巴细胞具有细胞毒性。人类免疫球蛋白M异种抗体在1月龄时可检测到。到2月龄时，这些天然抗猪异种抗体的血清水平达到与成人相当的水平，并产生与成人血清相似的细胞毒性。这些发现表明：（1）新生儿血清中不存在天然抗猪免疫球蛋白M异种抗体；（2）尽管存在能与猪内皮细胞和淋巴细胞结合的免疫球蛋白G异种抗体，但新生儿血清对猪内皮细胞和淋巴细胞无细胞毒性；（3）天然抗猪免疫球蛋白M异种抗体最早在1月龄时开始产生，到2月龄时其循环水平与成人相当。
