细胞间粘附分子—1和血管细胞粘附分子—1在慢性排斥反应中的 …

为了探讨移植肾慢性排斥反应的发病机制，应用免疫组化技术对１６例肾移植术后发生慢性排斥反应患者的移植肾组织及５例正常肾组织行细胞间粘附分子－１，血管细胞粘附分子－１染色及ＨＥ染色。结果表明ＩＣＡＭ－１，ＶＣＡＭ－１在正常肾脏和慢性排斥反应移植肾脏上的表达分布不同。结果提示，它们在移植肾慢性排斥反应的发生，发展过程中起重要的作用。     

血清可溶性细胞间粘附分子-1在肾移植监测中的价值

采用双抗体夹心酶联免疫法对８７例肾移植患者进行细胞间粘附分子１（ｃＩＣＡＭ１）动态监测，以探讨其在术后监测中的价值。结果发现，移植术后ｃＩＣＡＭ１水平短暂升高后即随移植肾功好转而下降，至术后两周达正常水平；急性排斥反应时ｃＩＣＡＭ１显著高于移植肾功稳定组及ＣｓＡ肾中毒组（Ｐ＜０．００１）；抗排斥治疗有效后，ｃＩＣＡＭ１又逐渐降至正常水平。结果表明，肾移植术后动态监测ｃＩＣＡＭ１的变化，不仅可早期诊断急性排斥反应并观察其治疗效果，而且有助于急性排斥反应与ＣｓＡ肾中毒的鉴别。     

细胞间粘附分子-1(ICAM-1)与肾脏移植排斥反应

ＩＣＡＭ－１是介导肾移植急性排斥反应的重要细胞粘附分子。肾移植急性排斥反应时肾脏组织ＩＣＡＭ－１表达增加，血、尿中可溶性的ＩＣＡＭ－１（ｓＩＣＡＭ－１）升高。动态监测肾移植术后患者血、尿中ｓＩＣＡＭ－１的变化，有助于肾移植急性排斥反应的诊断和抗排斥反应的疗效评价，应用ＩＣＡＭ－１单克隆抗体，可以提高肾移植成功率。     

血清可溶性血管细胞粘附分子—1测定在肾移植急性排斥反应 …

目的：探讨血清可溶性血管细胞粘附分子－１（ｓＶＣＡＭ－１）测定在肾移植术后免疫学监测中的价值。方法：采用酶联免疫吸附法（ＥＬＩＳＡ）动态监测５６例肾移植患者术后ｓＶＣＡＭ－１水平的变化。结果：肾移植患者术后ｓＶＣＡＭ－１水平呈规律性变化,急性排斥反应组ｓＶＣＡＭ－１水平明显高于移植肾功能稳定组和ＣｓＡ肾中毒组,差异有非常显著意义（Ｐ〈０．０１）。对激素治疗敏感的排斥反应患者,ｓＶＣＡＭ－１逐渐降至     

可溶性细胞间粘附分子—1和肿瘤坏死因子在监测肾移植排斥反应 …

目的 探讨血清可溶性细胞间粘附分子－１（ｓＩＣＡＭ－１）和肿瘤坏死因子（ＴＮＦ）在肾移植排斥反应监测中的意义。方法 采用双抗体夹心法和Ｌ９２９靶细胞法对４１例肾移植患者术后血清中ｓＩＣＡＭ－１和ＴＮＦ进行动态监测。结果 肾移植术后血清ｓＩＣＡＭ－１和ＴＮＦ出现相似的变化；术后肾功能稳定恢复组，环孢素Ａ（ＣｓＡ）肾中毒组与尿毒症组及正常对照组间血清ｓＩＣＡＭ－１和ＴＮＦ水平无显著性差异；当发生急性排     

大鼠移植肾组织ICAM-1/LFA-1分子表达与急性排斥反应的关系

目的探讨移植肾组织内细胞间粘附分子－１（ＩＣＡＭ－１）／淋巴细胞功能相关抗原－１（ＬＦＡ－１）的异常表达与移植排斥的关系。方法采用改进的大鼠原位肾移植模型，分五个实验组，在不同的时间段、观测受体鼠存活、肾功能；以及移植肾组织用单克隆抗体免疫组织化学染色后，图象分析法定量测定移植肾组织ＩＣＡＭ－１／ＬＦＡ－１分子表达的水平。结果移植肾急性排斥组ＩＣＡＭ－１／ＬＦＡ－１分子水平显著高于同品系移植对照组和药物治疗组。结论移植肾组织活检同时检测组织内ＩＣＡＭ－１／ＬＦＡ－１分子的表达，在肾移植急性排斥的诊断和治疗方面具有极其重要的临床意义。     

肝细胞肝癌细胞间粘附分子-1 mRNA表达的研究

寻找甲胎蛋白（ＡＦＰ）以外更新、更敏感的血清标记物是肝癌研究中的重要课题。近年有关细胞间粘附分子－１（ＩＣＡＭ－１）和肝细胞肝癌（ＨＣＣ）的研究提示,ＩＣＡＭ－１在ＨＣＣ病人组织及血清中（ｃＩＣＡＭ－１）呈高水平表达＾〔１,３〕。本研究通过检测ＨＣＣ组织中ＩＣＡＭ－１信使核糖核酸（ＩＣＡＭ－１ｍＲＮＡ）的表达,探讨血清中高水平ＩＣＡＭ－１与ＨＣＣ组织中ＩＣＡＭ－１ｍＲＮＡ的相互关系,为ｃＩＣＡＭ－测定在ＨＣＣ早期诊断及术后复发监测中的作用寻找理论依据。     

细胞间粘附分子—1（ICAM—1）与肾脏移植排斥反应

ＩＣＡＭ－１是介导肾移植急性排斥反应的重要细胞粘附分子。肾移植急性排斥反应时肾脏组织ＩＣＡＭ－１表达增加，血，尿中可溶性的ＩＣＡＭ－１同。动态监测肾移植术后患才血，尿中ｓＩＣＡＭ－１的变化，有助于肾移植急性排斥的诊断和抗排斥反应的疗效评价，应用ＩＣＡＭＰ－１单克隆抗体，可以提高肾移植成功率。     

肾移植后尿中可溶性细胞间粘附分子-1浓度监测的临床意义

目的：评价肾移植后患者尿中可溶性细胞间粘附分子－１（ｓＩＣＡＭ－１）浓度变化的临床意义。方法：动态检测２０例肾移植患者术后２个月内尿中ｓＩＣＡＭ－１浓度的变化。结果：急性排斥反应（ＡＲ）时,ｓＩＣＡＭ－１的升高较临床诊断提早数天,并且显著高于环孢素Ａ肾中毒组;对甲基氢化泼尼松敏感的排斥反应,抗排斥治疗数天后ｓＩＣＡＭ－１下降到排斥前水平。结论：肾移植术后动态监测受者尿中ｓＩＣＡＭ－１浓度有助于ＡＲ     

ICAM-1和VCAM-1测定在肾移植急性排斥反应中的临床意义

目的探讨血清可溶性细胞间粘附分子１（ｓＩＣＡＭ１）和可溶性血管细胞粘附分子１（ｓＶＣＡＭ１）在肾移植急性排斥反应中的临床意义。方法采用酶联免疫吸附法（ＥＬＩＳＡ）动态监测５６例肾移植患者术后ｓＩＣＡＭ１和ｓＶＣＡＭ１水平的变化。结果肾移植患者术后ｓＩＣＡＭ１和ｓＶＣＡＭ１水平呈规律性变化,急性排斥反应组ｓＩＣＡＭ１为（３９０．６±９１．０）ｎｇ／ｍｌ,ｓＶＣＡＭ１为（１９５７．１±４０３．１）ｎｇ／ｍｌ,明显高于移植肾功能稳定组的（１３７．３±１６．８）ｎｇ／ｍｌ、（１１１８．４±２１０．４）ｎｇ／ｍｌ和ＣｓＡ肾中毒组的（１３２．７±２４．８）ｎｇ／ｍｌ、（１２８５．８±２７０．５）ｎｇ／ｍｌ,差异有非常显著性（Ｐ＜０．０１）。结论ｓＩＣＡＭ１和ｓＶＣＡＭ１可以作为肾移植术后急性排斥反应的免疫学监测指标。     

急性排斥反应时CD15和血小板/内皮细胞粘附分子在移植肾的表达

应用免疫组织化学ＳＰ法和计算机图象分析系统观察分析了１８例急性排斥反应时移植肾活检标本中ＣＤ１５和血小板／内皮细胞粘附分子的表达情况，以探讨其变化的意义。     

An in vitro model of antibody-mediated injury to glomerular endothelial cells: Upregulation of MHC class II and adhesion molecules

Chronic active antibody-mediated rejection is a major cause of allograft failure in kidney transplantation. Microvascular inflammation and transplant glomerulopathy are defining pathologic features of chronic active antibody-mediated rejection and are associated with allograft failure. However, the mechanisms of leukocyte infiltration and glomerular endothelial cell injury remain unclear. We hypothesized MHC class II ligation on glomerular endothelial cells (GEnC) would result in upregulation of adhesion molecules and production of chemoattractants. A model of endothelial cell activation in the presence of antibodies to MHC classes I and II was used to determine the expression of adhesion molecules and chemokines. Murine GEnC were activated with IFNγ, which upregulated gene expression of β2-microglobulin (MHC class I), ICAM1, VCAM1, CCL2, CCL5, and IL-6. IFNγ stimulation of GEnC increased surface expression of MHC class I, MHC class II, ICAM1, and VCAM1. Incubation with antibodies directed at MHC class I or class II did not further enhance adhesion molecule expression. Multispectral imaging flow cytometry and confocal microscopy demonstrated MHC molecules co-localized with the adhesion molecules ICAM1 and VCAM1 on the GEnC surface. GEnC secretion of chemoattractants, CCL2 and CCL5, was increased by IFNγ stimulation. CCL2 production was further enhanced by incubation with sensitized plasma. Endothelial activation induces de novo expression of MHC class II molecules and increases surface expression of MHC class I, ICAM1 and VCAM1, which are all co-localized together. Maintaining the integrity and functionality of the glomerular endothelium is necessary to ensure survival of the allograft. IFNγ stimulation of GEnC propagates an inflammatory response with production of chemokines and co-localization of MHC and adhesion molecules on the GEnC surface, contributing to endothelial cell function as antigen presenting cells and an active player in allograft injury.     

The Impact of ICAM1 and VCAM1 Gene Polymorphisms on Chronic Allograft Nephropathy and Transplanted Kidney Function

ICAM-1 and VCAM-1 adhesion molecules play important roles in the immune response and emergence of chronic allograft nephropathy (CAN). The several polymorphisms of ICAM1 and VCAM1 genes are associated with changes in molecular expression therefore affecting allograft function and immune responses after kidney transplantation. The aim of this study was to examine the impact of polymorphisms in ICAM1 and VCAM1 genes on biopsy-proven CAN and renal allograft function. The 270 Caucasian renal transplant recipients (166 men and 104 women) were genotyped for the rs5498 ICAM1 and rs1041163 and rs3170794 VCAM1 gene polymorphisms using real-time polymerase chain reaction. There was no correlation between polymorphisms and CAN. Creatinine concentrations in the first month after transplantation differed between the rs5498 ICAM1 genotypes (P = .095), being higher for GG carriers (AA + AG vs GG, P =.07) albeit not with statistical significance. Creatinine concentrations at 12, 24, and 36 months after transplantation differed significantly among rs5498 ICAM1 genotypes (P = .0046, P =.016, and P = .02) and were higher among GG carriers (AA + AG vs GG, P = .001, P = .004, and P = .006). Rs5498 ICAM1 GG genotype and receipient male gender were independent factors associated with higher creatinine concentrations. These results suggest that the rs5498 ICAM1 GG genotype may be associated with long-term allograft function.     

Expression of cyclooxygenase-1 and cyclooxygenase-2 in human renal allograft rejection – a prospective study

Cyclooxygenases (COX) are known to be involved in inflammatory kidney diseases. However, there are no data available about the expression of COX-1 and only preliminary reports about the expression of COX-2 in biopsies of patients undergoing acute renal allograft rejection. We conducted this prospective study to analyze the expression, distribution, and cellular localization of COX-1 and -2 and thus to elucidate the role of COX in human kidney transplantation. One hundred forty-four biopsies were included from patients without rejection and unaltered morphology (n = 60), with acute interstitial rejection (n = 7), with acute vascular rejection (n = 21), with chronic allograft nephropathy (n = 16), without rejection but with various other lesions (n = 40). COX-1 and -2 expression was localized in each biopsy by immunohistochemistry. We found a highly significant up-regulation of COX-1 in vessels and in infiltrating interstitial cells of patients with acute allograft rejection compared with biopsies with well-preserved tissue. Also, COX-2 expression was significantly elevated in infiltrating interstitial cells of biopsies with acute rejection. This is the first prospective study demonstrating a significant induction of both COX-1 and -2 in human allograft biopsies with acute rejection after renal transplantation.     

SDF-1 expression is elevated in chronic human renal allograft rejection

The exact mechanism of acute and chronic allograft rejection still remains unclear. The chemokine SDF-1 as mediator of allograft rejection has been under intensive investigation in liver, cardiac and bone marrow transplantation, whereas in renal transplantation, there are no reports about SDF-1 to date. This study was performed to evaluate if SDF-1 might also play an important role in human renal graft biopsies. One hundred and ninety formalin-fixed, paraffin-embedded renal allograft biopsies were included in the analysis from patients with normal renal graft morphology (according to Banff 97 classification grade 1, n = 84), with acute interstitial rejection (Banff grade 4 type I, n = 10), with acute vascular rejection (Banff grade 4 type II, n = 21), with chronic allograft nephropathy (CAN, Banff grade 5, n = 23), and without rejection but with various other lesions (Banff grade 6, n = 42). SDF-1 was localized by immunohistochemistry. In biopsies with CAN, SDF-1 expression was significantly elevated in interstitial infiltrates and infiltrating neointimal cells of arteries compared with biopsies with normal renal graft morphology. This is the first study describing a role of SDF-1 in human renal allograft rejection. We were able to demonstrate in a large number of biopsies an upregulation of SDF-1 in patients with CAN. Whether SDF-1 has pro-inflammatory or protective properties in this setting has to be evaluated in further trials.     

bFGF及PDGFR表达与肾移植慢性排斥血管病变和肾小球损？…

目的 探讨碱性成纤维细胞生长因子（ｂＦＧＦ）及血小板源性生长因子受体（ＰＤＧＦＲ）的表达与肾移植慢性排斥反应血管病变及肾小球损伤之间的关系。方法 采用免疫组化ＳＰ法检测２３例排斥肾组织、１２例正常肾组织、１４例远离癌的正常肾组织血管及肾小球中ｂＦＧＦ及ＰＤＧＦＲ的表达。结果 ｂＦＧＦ及ＰＤＧＦＲ在排斥组织血管平滑肌细胞、内膜层及肾小球中的表达明显高于正常组织及癌组织（Ｐ〈均０．０１）。结论 ｂＦＧ     

Fas/FasL表达和细胞凋亡在人类同种异体移植肾急性排斥中的作用

目的探讨移植肾急性排斥（ＡＲ）时细胞凋亡与Ｆａｓ和Ｆａｓ配体（ＦａｓＬ）表达的作用及其临床意义。方法分别用原位末端标记技术（ＴＵＮＥＬ法）和免疫组织化学方法检测２６例移植肾ＡＲ标本中细胞凋亡和Ｆａｓ／ＦａｓＬ表达情况。结果细胞凋亡和Ｆａｓ／ＦａｓＬ表达主要在ＡＲ移植肾小管上皮发生,且凋亡指数和Ｆａｓ／ＦａｓＬ表达与肾组织病理损伤程度平行,与正常肾对照组和移植肾功能稳定组比较差异显著（Ｐ＜０．０１）。结论肾小管上皮细胞凋亡在ＡＲ所致的移植肾损伤中起重要作用,Ｆａｓ／ＦａｓＬ系统可能参与移植肾ＡＲ,是造成肾小管上皮细胞凋亡的重要因素。ＴＵＮＥＬ法检测细胞凋亡可作为判断移植肾病理变化和预后的重要指标     

Induction of RANTES, HLA-DR, and intercellular adhesion molecule-1 on highly purified distal tubular cells from human kidney

BACKGROUND: Expression of proinflammatory molecules by tubular epithelial cells plays an important role in renal allograft rejection and inflammatory kidney diseases. Different studies from patients with acute rejection point to the involvement of distal tubular segments. At present no in vitro system for the human distal tubule is established. METHODS: Human distal tubular cells were isolated immunomagnetically. Cultured cells were stimulated with cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-1beta, or a cytokine mix). Secretion of RANTES (regulated upon activation, normal T-cell expressed and secreted) was evaluated with an enzyme-linked immunoassay. Expression of HLA-DR and intercellular adhesion molecule (ICAM)-1 was assessed by flow cytometric analysis and immunofluorescence studies. RESULTS: Our data clearly indicate that distal tubular cells express RANTES, HLA-DR, and ICAM-1 in response to a mixture of specific cytokines. Dexamethasone inhibited the induced expression of RANTES and HLA-DR significantly, but not that of ICAM-1. CONCLUSIONS: We demonstrate an appropriate in vitro system for the human distal tubule. The present study proves the involvement of the distal tubular segment during inflammatory kidney diseases.     

移植肾慢性排斥组织中血小板源性生长因子受体表达研究

目的探讨生长因子在同种异体肾移植慢性排斥反应肾组织中的表达、分布及临床意义。方法采用免疫组化ＳＰ法研究１２例正常肾、１４例肾癌旁及２３例慢性排斥肾组织中血小板源性生长因子受体（ＰＤＧＦＲ）表达。结果排斥肾组织ＰＤＧＦＲ表达阳性率为９１％，明显高于正常组织及癌旁组织（２５％，２８％），差异有显著性，ＰＤＧＦＲ主要表达于血管平滑肌、肾小球膜、肾小管等细胞的胞浆、胞膜及核膜。结论ＰＤＧＦＲ表达可调控正常肾组织，高表达与慢性排斥密切相关；未发现ＰＤＧＦＲ表达与临床症状相关。     

Glomerulonephritis is the major cause of proteinuria in renal transplant recipients: histopathologic findings of renal allografts with proteinuria

The proteinuria in renal allograft recipients has been regarded as a sign of poor prognosis. The causes of post-transplant proteinuria include chronic rejection, chronic transplant glomerulopathy, glomerulonephritis (GN), acute rejection, and cyclosporine nephrotoxicity. Among them, chronic rejection is known to be most frequent. We analyzed the histopathologic findings of renal allograft biopsies in 197 Korean recipients with proteinuria. Among them, 26 patients developed proteinuria over 500 mg/d. All patients received baseline immunosuppression with cyclosporine. From 26 patients with post-transplant proteinuria, 29 biopsies were performed and their histologic diagnoses were immunoglobulin A nephropathy (IgAN) in 17, IgAN combined with chronic allograft nephropathy in 1, focal segmental glomerulosclerosis in 2, crescentic GN in 1, membranous GN in 1, diabetic nephropathy in 1, acute tubulointerstitial nephritis in 1, and chronic rejection in 3 biopsies. The remaining two biopsies showed nonspecific findings. The most common cause of post-transplant proteinuria was IgAN (62% of biopsies). The incidence of chronic rejection was relatively low and predominant cyclosporine-associated changes were not observed. In conclusion, our data suggest that the main causes of post-transplant proteinuria in Korea are primary glomerulonephritides rather than chronic rejection or cyclosporine nephrotoxicity, and the kidney allograft biopsies from patients with proteinuria should be handled as native kidney.