Suramin inhibits antibody binding to cell surface antigens and disrupts complement-mediated mesangial cell lysis.
Suramin inhibits antibody binding to cell surface antigens and disrupts complement-mediated mesangial cell lysis.
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DOI：
10.1016/j.jphs.2016.03.011
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发表时间：
2016-12
影响因子：
3.5
通讯作者：
Honglan Piao;Yuan Chi;Xiling Zhang;Zhen Zhang;Kun Gao;M. Niimi;M. Kamiyama;Jinming Zhang;M. Takeda;Jian Yao
中科院分区：
文献类型：
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作者：
Honglan Piao;Yuan Chi;Xiling Zhang;Zhen Zhang;Kun Gao;M. Niimi;M. Kamiyama;Jinming Zhang;M. Takeda;Jian Yao
苏拉明抑制免疫反应，保护细胞免受炎性细胞损伤。然而，人们对其机制知之甚少。采用抗体+补体诱导肾小球系膜细胞(MC)溶解的体外模型，探讨苏拉明对免疫细胞损伤的保护作用及其机制。大鼠肾小球系膜细胞暴露于抗Thy-1抗体加补体或抗MC兔血清可引起补体依赖性细胞溶解，这种作用可被苏拉明及其结构类似物NF023和NF049阻断，但不能被嘌呤能受体拮抗剂PPADS阻断。外源ATP的加入也不影响MC的裂解。进一步的分析表明，苏拉明干扰了抗体与细胞膜抗原的结合，并抑制了抗体诱导的几种蛋白质的磷酸化，包括p38。用化学抑制剂抑制p38可显著减轻细胞损伤。总之，我们的结果表明，苏拉明通过抑制抗体与细胞表面抗原的结合和抑制p38的激活来保护细胞免受抗体启动和补体依赖的细胞损伤。因此，我们的研究为苏拉明的作用提供了新的机制见解，并提示苏拉明可能用于治疗某些免疫性疾病。
Suramin inhibits immune responses and protects cells against inflammatory cell injury. However, little is known about its mechanisms. Using anin vitromodel of glomerular mesangial cell (MC) lysis induced by antibodies plus complement, we investigated the potential protective effects and mechanisms of suramin on immunologic cell injury. Exposure of rat MCs to anti-Thy-1 antibody plus complement or anti-MC rabbit serum caused complement-dependent cell lysis, which was blocked by suramin and its structural analogue NF023 and NF049, but not by PPADS, an antagonist of purinergic receptors. Addition of exogenous ATP also failed to affect MC lysis. Further analysis revealed that suramin interfered with antibody binding to cell membrane antigens and suppressed antibody-induced phosphorylation of several proteins, including p38. Inhibition of p38 with chemical inhibitor significantly attenuated cell injury. Collectively, our results indicate that suramin protects cells against antibody-initiated and complement-dependent cell injury through inhibition of antibody binding to cell surface antigens and suppression of p38 activation. Our study thus provides novel mechanistic insights into the actions of suramin and suggests that suramin might be used to treat certain immune diseases.