Thrombotic thrombocytopenic purpura and sporadic hemolytic-uremic syndrome plasmas induce apoptosis in restricted lineages of human microvascular endothelial cells
Thrombotic thrombocytopenic purpura and sporadic hemolytic-uremic syndrome plasmas induce apoptosis in restricted lineages of human microvascular endothelial cells
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DOI：
10.1182/blood.v89.4.1224
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发表时间：
1997-02-15
期刊：
影响因子：
20.3
通讯作者：
Laurence, J
中科院分区：
文献类型：
--
作者：
Mitra, D;Jaffe, EA;Laurence, J
血栓性血小板减少性紫癜（TTP）和散发性溶血性尿毒症综合征（HUS）是在没有炎症反应的情况下发生的血栓性微血管病。TTP/散发性HUS所涉及的组织的超微结构特征提示了凋亡过程。与这些发现一致，我们观察到TTP血浆诱导真皮微血管而非脐静脉来源的原代人内皮细胞（EC）的凋亡（Laurence等，Blood 87：3245，1996）。我们现在记录了TTP和散发性HUS患者的血浆诱导微血管EC受限谱系中细胞凋亡和凋亡相关分子Fas（CD 95）表达的能力，但未记录来自儿童/哮喘相关HUS患者的血浆。小血管真皮，肾脏和大脑起源的EC容易诱导Fas和凋亡细胞死亡。相反，肺和肝起源的微血管EC以及大血管、冠状动脉的EC对这两个过程都有抵抗力。这种二分法与TTP/散发性HUS的体内病理学相似，肺和肝微血管系统明显保留。凋亡EC也具有促凝血表型的一些特征，包括前列腺素12（前列环素）的抑制产生。这些现象支持TTP中微血管EC凋亡的病理生理学意义，将其扩展到相关疾病（散发性HUS），并建议在这些综合征的实验治疗中考虑凋亡抑制剂。(C)1997年，美国血液学会。
Thrombotic thrombocytopenic purpura (TTP) and sporadic hemolytic-uremic syndrome (HUS) are thrombotic microangiopathies that occur in the absence of an inflammatory response. Ultrastructural features of tissues involved in TTP/sporadic HUS suggest an apoptotic process. Consistent with these findings, we observed that TTP plasmas induce apoptosis in primary human endothelial cells (EC) of dermal microvascular but not umbilical vein origin (Laurence et al, Blood 87:3245, 1996). We now document the ability of plasmas from both TTP and sporadic HUS patients, but not from a patient with childhood/diarrhea-associated HUS, to induce apoptosis and expression of the apoptosis-associated molecule Fas (CD95) in restricted lineages of microvascular EC. EC of small vessel dermal, renal, and cerebral origin were susceptible to induction of Fas and an apoptotic cell death. In contrast, microvascular EC of pulmonary and hepatic origin, as well as EC of a large vessel, coronary artery, were resistant to both processes. This dichotomy parallels the in vivo pathology of TTP/sporadic HUS, with notable sparing of the pulmonary and hepatic microvasculature. Apoptotic EC also had some features of a procoagulant phenotype, including depressed production of prostaglandin 12 (prostacyclin). These phenomena support the pathophysiologic significance of microvascular EC apoptosis in TTP, extend it to a related disorder (sporadic HUS), and suggest consideration of apoptosis inhibitors in the experimental therapeutics of these syndromes. (C) 1997 by The American Society of Hematology.