Synergism between platelets and leukocytes in inducing endothelial cell apoptosis in the cold ischemic rat liver: a Kupffer cell-mediated injury
Synergism between platelets and leukocytes in inducing endothelial cell apoptosis in the cold ischemic rat liver: a Kupffer cell-mediated injury
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DOI：
10.1096/fj.00-0554fje
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发表时间：
2001-05-01
期刊：
影响因子：
4.8
通讯作者：
Clavien, PA
中科院分区：
文献类型：
--
作者：
Sindram, D;Porte, RJ;Clavien, PA
肝窦内皮细胞凋亡是肝移植术后早期再灌注损伤的标志。血小板隔离发生在移植后并引起SEC凋亡。白细胞在再灌注时也粘附于肝脏。它们在诱导SEC凋亡中的作用及其与血小板的相互作用尚不清楚。枯否细胞可能与循环细胞相互作用，因此，它们可能参与诱导SEC凋亡。我们检验了血小板和白细胞通过枯否细胞依赖性机制协同诱导SEC凋亡的假设。将肝脏在冷的威斯康星州大学溶液中保存24 h，并在分离的灌注大鼠肝脏模型中用含有红细胞和血小板、白细胞或两者的灌注液进行再灌注。在一些实验中，枯否细胞被氯化钆或戊茶碱抑制。再灌注后，通过末端脱氧核苷酸转移酶介导的缺口末端标记和电子显微镜测定细胞凋亡。白细胞和血小板迅速被隔离到肝脏中并诱导SEC凋亡。血小板和白细胞粘附的存在与SEC细胞凋亡的急剧增加相关联，与使用一个循环元素群体或在血小板和白细胞均不存在的情况下进行肝脏再灌注相比。在用血小板和白细胞再灌注的肝脏中，SEC细胞凋亡被枯否细胞抑制的任一方式完全废除。血小板和白细胞通过枯否细胞依赖性机制诱导冷保存肝脏再灌注后SEC凋亡。
Sinusoidal endothelial cell (SEC) apoptosis is the hallmark of early reperfusion injury in liver transplantation. Platelet sequestration occurs after transplantation and causes SEC apoptosis. Leukocytes also adhere to the liver upon reperfusion. Their role and interaction with platelets in inducing SEC apoptosis are unknown. Kupffer cells possibly interact with circulating cells; therefore, they could be involved in inducing SEC apoptosis. We tested the hypothesis that platelets and leukocytes synergistically induce SEC apoptosis through a Kupffer‐cell‐dependent mechanism. Livers were preserved for 24 h in cold University of Wisconsin solution and were reperfused in an isolated perfused rat liver model with perfusate containing red blood cells and either platelets, leukocytes, or both. In some experiments, Kupffer cells were inhibited by either gadolinium chloride or pentoxifylline. Apoptosis was determined after reperfusion by terminal deoxynucleotidyl transferase‐mediated nick‐end labeling and electron microscopy. Leukocytes and platelets were rapidly sequestered into the liver and induced SEC apoptosis. The presence of both platelet and leukocyte adhesion was associated with a dramatic increase in SEC apoptosis compared with liver reperfused with the use of one population of circulating elements or in absence of both platelets and leukocytes. In liver reperfused with platelets and leukocytes, SEC apoptosis was completely abrogated by either modality of Kupffer cell inhibition. Platelets and leukocytes induce SEC apoptosis upon reperfusion of cold preserved liver through a Kupffer‐cell‐dependent mechanism.