Briscoe D M, Yeung A C, Schoen F J, Allred E N, Stavrakis G, Ganz P, Cotran R S, Pober J S, Schoen E L
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
Transplantation. 1995 Jan 27;59(2):204-11.
We conducted a prospective longitudinal study to determine the clinical significance of endothelial adhesion molecule expression in endomyocardial biopsies from human cardiac allografts. Ten to 18 (mean 13) consecutive allograft biopsies were obtained from 20 serial human transplant recipients over a one-year period. A total of 267 biopsies was examined. The expression of endothelial adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, as well as the presence of CD3+ T cell infiltrates was assessed by immunocytochemical staining of frozen sections. Separate specimens taken at the same time were analyzed histologically for ischemic injury or rejection. ICAM-1--and, to a lesser extent VCAM-1--was expressed at low levels in normal biopsies. E-selectin was only expressed in 15% of histologically normal biopsy specimens. Ischemic injury noted in the immediate posttransplant period was associated with increased expression of all three adhesion molecules. VCAM-1 expression increased both with the degree of CD3+ T cell infiltrates (P < 0.001) and with the degree of rejection (P < 0.05). ICAM-1 increased over constitutive levels in association with diffuse CD3+ infiltrates (P < 0.001) and with rejection (P < 0.05). E-selectin was increased on occasional vessels in association with CD3+ infiltrates (P < 0.001), but was not associated with active rejection. Increases in E-selectin were most likely to occur in biopsies just prior to rejection episodes (odds ratio 3.3), and were least likely to occur in biopsies following rejection (odds ratio 0.3). ICAM-1, but not VCAM-1, was also elevated in prerejection specimens. VCAM-1 and ICAM-1 declined in postrejection specimens. These data suggest a dynamic pattern in the expression of endothelial cell adhesion molecules during the course of cardiac allograft rejection. This study also suggests that endothelial E-selectin expression may be a useful clinical marker of impending rejection. Finally, inducible VCAM-1 expression may be a helpful adjunct in the diagnosis of ongoing acute rejection, and decreases in its expression may be indicative of successful antirejection therapy.
我们进行了一项前瞻性纵向研究，以确定人心脏同种异体移植心肌内膜活检中内皮黏附分子表达的临床意义。在一年时间内，从20例连续的人类移植受者中获取了10至18次（平均13次）连续的同种异体移植活检样本。共检查了267份活检样本。通过对冰冻切片进行免疫细胞化学染色，评估内皮黏附分子细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）和E-选择素的表达，以及CD3+ T细胞浸润情况。同时采集的单独标本进行组织学分析，以评估缺血性损伤或排斥反应。在正常活检样本中，ICAM-1以及在较小程度上VCAM-1以低水平表达。E-选择素仅在15%的组织学正常活检标本中表达。移植后即刻出现的缺血性损伤与所有三种黏附分子的表达增加有关。VCAM-1的表达随着CD3+ T细胞浸润程度（P < 0.001）和排斥反应程度（P < 0.05）的增加而增加。ICAM-1与弥漫性CD3+浸润（P < 0.001）和排斥反应（P < 0.05）相关，其表达超过基础水平。E-选择素在偶尔的血管中与CD3+浸润相关增加（P < 0.001），但与急性排斥反应无关。E-选择素增加最有可能发生在排斥反应发作前的活检样本中（优势比3.3），而在排斥反应后的活检样本中发生的可能性最小（优势比0.3）。在排斥反应前的标本中，ICAM-1升高，而VCAM-1未升高。排斥反应后的标本中，VCAM-1和ICAM-1下降。这些数据表明心脏同种异体移植排斥反应过程中内皮细胞黏附分子表达呈动态模式。本研究还表明内皮E-选择素表达可能是即将发生排斥反应的有用临床标志物。最后，诱导性VCAM-1表达可能有助于诊断正在进行的急性排斥反应，其表达下降可能表明抗排斥治疗成功。
