Ligation of HLA class I molecules on smooth muscle cells with anti-HLA antibodies induces tyrosine phosphorylation, fibroblast growth factor receptor expression and cell proliferation
Ligation of HLA class I molecules on smooth muscle cells with anti-HLA antibodies induces tyrosine phosphorylation, fibroblast growth factor receptor expression and cell proliferation
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DOI：
10.1093/intimm/10.9.1315
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发表时间：
1998-09-01
影响因子：
4.4
通讯作者：
Reed, EF
中科院分区：
文献类型：
--
作者：
Bian, H;Harris, PE;Reed, EF
移植动脉粥样硬化的发展是慢性排斥反应的一种表现，是心脏和肾脏同种异体移植物长期存活的主要障碍。移植后产生抗供体 HLA 抗体的移植受者的移植动脉粥样硬化发病率增加，表明抗 HLA 抗体在该疾病的发病机制中发挥作用。我们假设抗HLA抗体通过与移植物的内皮和平滑肌上的I类分子结合并转导刺激细胞增殖的信号来介导移植动脉粥样硬化的发展。在本报告中，我们证明抗 HLA I 类抗体可在平滑肌细胞中转导信号，刺激细胞内蛋白质酪氨酸磷酸化的增加和成纤维细胞生长因子 (FGF) 受体的上调。与平滑肌细胞上的 I 类分子结合的抗体还伴随着对碱性 FGF 的反应性增加和细胞增殖增强。这些发现可以解释产生抗供体 HLA 抗体的受者中移植动脉粥样硬化发生率增加的原因。
The development of transplant atherosclerosis, a manifestation of chronic rejection, is the major obstacle to long-term survival of cardiac and renal allografts. The incidence of transplant atherosclerosis is increased in transplant recipients producing antidonor HLA antibodies following transplantation, suggesting that anti-H LA antibodies play a role in the pathogenesis of the disease. We have postulated that anti-HLA antibodies mediate the development of transplant atherosclerosis by binding to class I molecules on the endothelium and smooth muscle of the graft and transducing signals which stimulate cell proliferation. In this report we demonstrate that anti-HLA class I antibodies transduce signals in smooth muscle cells stimulating increased tyrosine phosphorylation of intracellular proteins and up-regulation of fibroblast growth factor (FGF) receptors. Antibody binding to class I molecules on smooth muscle cells is also accompanied by increased responsiveness to basic FGF and augmented cell proliferation. These findings may explain the increased occurrence of transplant atherosclerosis in recipients producing anti-donor HLA antibodies.