Dorling A, Delikouras A, Nohadani M, Polak J, Lechler R I
Department of Immunology, Imperial College School of Science, Technology and Medicine, Hammersmith Hospital, London, Great Britain.
Xenotransplantation. 1998 Feb;5(1):84-92. doi: 10.1111/j.1399-3089.1998.tb00013.x.
Transplanted xenografts, protected from rejection by depletion of xenoreactive natural antibodies (XNA) and complement, can sometimes survive when complement levels and titres of anti-graft antibodies return to baseline; this phenomenon is called accommodation. We have previously reported that low concentrations of human IgG induce a change in the phenotype of immortalised porcine endothelial cells (IPEC) consistent with the development of accommodation. The cells acquired a resistance to lysis by human complement and showed a reduced expression of VCAM. In this study, we extend these findings by showing that VCAM expression falls on several IPEC clones and on primary porcine endothelial cells. Moreover, we show that these accommodated cells bind fewer human lymphocytes compared to controls, implying that leukocyte traffic through accommodated endothelium may be altered compared to that through normal endothelium. Finally we show that during the induction of accommodation, porcine endothelial cells produce greater amounts of nitric oxide than controls, due to the expression of inducible nitric oxide synthase (iNOS). We speculate that nitric oxide may be an important mediator in accommodation.
通过去除异种反应性天然抗体（XNA）和补体来防止排斥反应的移植异种移植物，在补体水平和抗移植物抗体滴度恢复到基线时，有时能够存活；这种现象被称为适应性改变。我们之前曾报道，低浓度的人IgG会诱导永生化猪内皮细胞（IPEC）的表型发生变化，这与适应性改变的发展一致。这些细胞获得了对人补体裂解的抗性，并显示血管细胞黏附分子（VCAM）的表达降低。在本研究中，我们通过证明VCAM在多个IPEC克隆和原代猪内皮细胞上的表达下降，扩展了这些发现。此外，我们还表明，与对照相比，这些适应性改变的细胞结合的人淋巴细胞更少，这意味着与通过正常内皮细胞相比，通过适应性改变的内皮细胞的白细胞运输可能会发生改变。最后，我们表明，在适应性改变的诱导过程中，由于诱导型一氧化氮合酶（iNOS）的表达，猪内皮细胞产生的一氧化氮比对照更多。我们推测一氧化氮可能是适应性改变中的一种重要介质。
