Antibodies fluted from acutely rejected renal allografts bind to and activate human endothelial cells
Antibodies fluted from acutely rejected renal allografts bind to and activate human endothelial cells
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DOI：
10.1016/s0198-8859(00)00109-9
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发表时间：
2000-05-01
期刊：
影响因子：
2.7
通讯作者：
Glotz, D
中科院分区：
文献类型：
--
作者：
Lucchiari, N;Panajotopoulos, N;Glotz, D
本研究旨在探讨抗内皮抗体（EAbs）如何参与急性不可逆肾移植排斥反应。25例因不可逆排斥反应（n = 22）和肾静脉血栓形成（对照组n = 3）而丢失的同种异体肾移植的洗脱液与培养的人脐静脉内皮细胞（HUVEC）进行了对照试验。所有患者在行肾切除术时均处于免疫抑制状态。通过流式细胞术（FACS）和半定量RT-PCR分析EAbs与粘附分子ELAM-1和VCAM-1的结合和膜表达。在移植时，以及在肾切除术前后，通过使用最敏感的技术进行特异性交叉配型的阴性，确定缺乏针对供者的抗hla抗体。从8个与HUVEC结合的排斥肾脏中洗脱的EAbs。它们没有诱导任何细胞毒性，但与HUVEC孵育（37℃，2.5 mg/ml） 4小时后，与对照EAbs相比，编码VCAM-1的mrna（增加35- 60倍）和ICAM-1的mrna（增加8- 12倍）上调，粘附分子的膜表达也显著增加，孵育后80%的细胞表达VCAM-1, 65%表达ELAM-1。急性血管排斥反应肾丢失的9例洗脱液中有8例（88.8%）检测到EAbs，而其他类型排斥反应肾丢失的13例（0.0%）中没有一例（p < 0.0001）检测到EAbs。我们的结论是，能够激活人内皮细胞的EAbs可以从急性排斥肾脏中恢复，并可能在急性排斥的发病机制中发挥直接作用。人类免疫学61,518-527（2000）。(C)美国组织相容性和免疫遗传学学会，2000。Elsevier Science Inc.出版。
This study was designed co investigate how antiendothelial antibodies (EAbs) are involved in acute irreversible renal graft rejection. Eluates from 25 renal allografts, lost by irreversible rejection (n = 22) and by renal vein thrombosis (controls n = 3), were tested against a panel of cultured human umbilical vein endothelial cells (HUVEC). All patients were under immunosuppression at the time of nephrectomy. EAbs binding and membrane expression of adhesion molecules ELAM-1 and VCAM-1 were analyzed by flow cytometry (FACS) and by semiquantitative RT-PCR for mRNAs coding for those molecules. The absence of anti-HLA antibodies against the donor was ascertained at transplant, and before and after nephrectomy by the negativity of specific crossmatches performed using the most sensitive techniques. EAbs eluted from eight rejected kidneys bound to HUVEC. They did not induce any cytotoxicity, but their incubation with HUVEC (4 h at 37 degrees C; 2.5 mg/ml) led to upregulation of mRNAs coding for VCAM-1 (35- to 60-fold increases) and ICAM-1 (8- to 12-fold increases) as compared with control EAbs, Membrane expression of adhesion molecules was also strikingly increased, with 80% of the cells expressing VCAM-1 and 65% expressing ELAM-1 upon incubation. EAbs were detected in eight out of nine (88.8%) eluates from kidneys lost from acute vascular rejection, but in none of the 13 (0.0%) kidneys lost from other types of rejection (p < 0.0001). We conclude that EAbs, capable of activating human endothelial cells, can be recovered from acutely rejected kidneys and may play a direct role in the pathogenesis of acute rejection. Human Immunology 61, 518-527 (2000). (C) American Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.