慢性乙型肝炎肝内浸润淋巴细胞功能相关抗原-1表达在肝细胞损伤及病毒清除中的意义

探讨淋巴细胞功能相关抗原—1(LFA-1）在慢性乙肝组织中浸润淋巴细胞的表达及意义。利用免疫组化技术，对51例不同类型的慢性HBV感染者肝组织内浸润淋巴细胞LFA-1的表达状况进行观察，并同时检测肝内HBcAg表达状况。慢性HBV感染者肝内浸润淋巴细胞存在不同程度的LFA-1表达，9例HBV感染的无症状携带者，肝内散在的淋巴细胞未见LFA-1表达，在42例慢性乙性肝炎中，其中38例肝组织浸润淋巴细胞LFA-1表达，阳性率为90．4％。阳性表达的淋巴细胞多位于肝组织病变明显区域及其周围肝组织，LFA-1表达强度与肝炎的程度有关，其中慢性重度乙型肝炎浸润淋巴细胞LFA—1表达较慢性中度乙型肝炎显著增强，慢性中度乙型肝炎LFA-1表达较慢性轻度乙型肝炎显著增强。肝内浸润淋巴细胞LFA-1表达阳性组、强阳性组较弱阳性及阴性组相比，肝内HBcAg阳性表达减少。慢性乙肝组织中浸润淋巴细胞LFA-1的表达参与了乙型肝炎的发病过程，不仅参与肝细胞的损害过程，同时亦有助于对肝细胞内HBV的清除。     

细胞间黏附分子—1／淋巴细胞功能相关抗原—1在乙型肝炎？…

目的 探讨细胞间黏附分子－１／淋细胞功能相关抗原－１（ＩＣＡＭ－１／ＬＦＡ－１）在乙型肝炎发病机制中的作用。方法 用免疫组化检测１１例正常人和７０例ＨＢＶ感染者肝内ＩＣＡＭ－１、ＬＦＡ－１和ＣＤ８表达状况，并用免疫组化双重染色技术研究ＨＢＶ感染者肝内ＩＣＡＭ－１与ＬＦＡ－１双重表达状况。结果 在炎症坏死区，ＬＦＡ－１阳性淋巴浸润在ＩＣＡＭ－１阳性肝细胞周围，部分与ＩＣＡＭ－１阳性肝细胞紧密接触，Ｌ     

慢性乙型肝炎肝组织ICAM-1 mRNA和ICAM-1表达及意义

目的探讨肝组织间粘附分子-1(ICAM-1)表达在慢性乙型肝炎(CHB)发病机理中的作用。方法用原位杂交和免疫组织化学技术检测11例正常人和50例慢性HBV感染者肝内ICAM-1 mRNA和ICAM-1表达情况。结果正常人和慢性无症状HBsAg携带者肝细胞无ICAM-1mRNA和ICAM-1表达,CHB患者肝细胞ICAM-1 mRNA和ICAM-1表达增强,阳性肝细胞多分布在汇管区周围和腺泡内炎症坏死区域;重度CHB患者肝细胞ICAM-1 mRNA和ICAM-1表达显著强于中、轻度CHB患者(P<0.05);肝细胞ICAM-1表达强度与肝组织炎症活动度呈显著正相关,p<0.01;肝细胞ICAM-1表达强的患者肝功能显著差于ICAM-1表达弱者,P<0.05。结论肝细胞ICAM-1表达在慢性乙型肝炎肝细胞坏死中起重要作用,肝细胞ICAM-1表达水平能较好反映其肝损害程度和肝功能状况。     

乙型肝炎肝内ICAM-1和HLA-DR表达及意义

乙型肝炎发病机制主要包括细胞毒性T淋巴细胞(CTL)介导的肝细胞损伤坏死和肝细胞凋亡。CD4阳性Th1细胞也可引起肝细胞凋亡。细胞间粘附分子-1(ICAM-1)系免疫球蛋白超家族成员,与其配体淋巴细胞功能相关抗原-1(LFA1)参与介导淋巴细胞与靶细胞及淋巴细胞间的粘附。国内外研究表明,ICAM-1在病毒性肝炎、内毒素血症所致肝损坏死、缺血后再灌流所致肝损伤、自身免疫性肝损伤及酒精性肝损伤中起重要作用。人白细胞抗原(HLA)Ⅱ类分子在乙     

透析相关性淀粉样变关节滑膜组织黏附分子和趋化因子的表达

目的　探讨透析相关性淀粉样变 (DRA)关节滑膜单核 /巨噬细胞浸润的机制。方法关节组织取自 12例长期血透病人的尸检标本 ,用单克隆抗体免疫组化法观察滑膜组织各种黏附分子和趋化因子的表达 ,以 2例活动性类风湿性关节炎和 3例正常人滑膜组织作为阳性和阴性对照。结果　合并DRA的血透病人血管内皮细胞表达细胞间黏附分子 1(ICAM 1)和 (或 )血管细胞黏附分子 1(VCAM 1)、E 选择素 ,滑膜细胞表达ICAM 1和单核细胞趋化蛋白 1(MCP 1) ,多数血管周围浸润的单核细胞LFA 1和VLA 4阳性。黏附分子和MCP 1表达的部位和程度与DRA的病程及单核细胞浸润程度密切相关。无DRA的血透病人和正常人滑膜组织中无明显黏附分子和趋化因子表达。结论滑膜组织表达黏附分子和MCP 1是DRA时关节组织单核 /巨噬细胞浸润的可能机制。     

细胞黏附分子-1在急性髓性白血病细胞与内皮细胞黏附中的作用

目的　检测急性髓性白血病 (AML)细胞与内皮细胞的黏附及细胞黏附分子 1(ICAM 1)及其配体淋巴细胞功能相关抗原 1(LFA 1)在黏附中的作用。方法　观察AML细胞与静止内皮细胞和肿瘤坏死因子α(TNFα)激活的内皮细胞的黏附 ;AML细胞与内皮细胞混合培养 2 4h的黏附 ;正常中性粒细胞与AML细胞培养上清作用 2 4h后的内皮细胞的黏附 ;流式和ELISA方法检测AML细胞培养上清作用后内皮细胞ICAM 1及可溶性ICAM 1的表达 ;并用ICAM 1和LFA 1的抗体进行阻滞黏附试验。结果　AML细胞与静止的内皮细胞黏附较少 (2 4 33± 2 87) % ,AML细胞与TNFα激活的内皮细胞的黏附 ,与内皮细胞混合培养 2 4h后的黏附以及正常中性粒细胞与AML细胞培养上清作用后内皮细胞的黏附明显增加 ,分别为 (81 87± 4 0 8) % ,(82 0 6± 7 0 5 ) % ,(83 99± 3 86 ) % (n =2 1,P <0 0 0 1) ;静止的内皮细胞ICAM 1及可溶性ICAM 1的表达分别为 (5 5 81± 4 11) %和 (0 839± 0 2 36 )μg/L ;AML细胞培养上清作用后内皮细胞ICAM 1及可溶性ICAM 1的表达明显增加 ,分别为 (6 5 36±5 97) %和 (1 4 2 4± 0 4 6 9) μg/L(n =2 1,P <0 0 5 ) ;用ICAM 1及LFA 1的抗体进行黏附阻滞后 ,AML细胞与TNFα激活的内皮细胞的黏附下降为 (2 0 12±     

HLA-ABC,HLA-DR,ICAM-1在乙型肝炎肝细胞表达的意义

为进一步探讨HLA-ABC.HIA-DR.ICAM-1在乙型肝炎肝细胞损伤中的作用.利用标记链菌素亲生物蛋白(LSAB)法对98例乙型肝炎肝穿组织进行HLA-ABC,HLA-DR,ICAM-1检测。结果显示HLA-ABC,ICAM-1在乙型肝炎肝细胞存在广泛表达,且与肝脏病变程度有关,HLA-DR也有一定程度表达,其阳性率分别为85.7％,83.7％,26.5％。阳性表达多位于肝细胞炎性病变或坏死区,常伴有不同程度炎性细胞浸润。提示HLA-ABC,ICAM-1的在肝细胞广泛表达在乙型肝炎发病中起重要作用。HLA-DR异常表达也一定程度参与了乙肝发病。这些免疫有关分子为T淋巴细胞识别杀伤HBV感染肝细胞提供了必要的分子基础,不仅与乙型肝炎肝细胞损伤有关,而且对肝内病毒的清除可能有一定的作用。     

慢性乙型肝炎患者肝组织ICAM-1的表达及sICAM-1水平

细胞间粘附分子 1(intercellularadhesionmolecule 1、ICAM 1)是免疫球蛋白超家族成员之一 ,血清ICAM 1(sICAM 1)与肝组织炎症活动度及肝细胞损伤程度密切相关。我们观察了慢性乙型肝炎患者肝组织ICAM 1的表达 ,同时测定sICAM 1水平 ,以探讨ICAM 1在慢性乙型肝炎发病机制中的作用。材料与方法一、病例我院 2 0 0 0年 5月～ 2 0 0 1年 4月经过肝穿刺活检确诊的 60例慢性乙型肝炎住院患者。男性 45例 ,女性 15例。年龄最大5 3岁 ,最小 17岁。其中慢性轻度 19例 ,中度 16例 ,重度 17例 ,慢性重型 8例。临床与病理诊断符合 2 0 0 0…     

脑缺血时细胞间黏附分子-1的表达与调控

文章综述了脑缺血时细胞间黏附分子 1(ICAM 1)的表达及作用、影响其表达的因素及ICAM 1抗体的应用 ,旨在探讨脑缺血的发病机制和寻找减轻脑缺血损伤的药物。     

细胞间黏附分子-1和淋巴细胞功能相关抗原-1在干燥综合征发病中的作用

目的探讨细胞间黏附分子（ICAM）-1和淋巴细胞功能相关抗原（LFA）-1在干燥综合征（SS）的发病机制中的作用。方法用免疫组织化学SABC法，3，3-二氨基联苯胺（DAB）显色，对32例不同程度干燥综合征患者唇腺组织和15名正常对照组进行了ICAM-1和LFA-1的检测。结果①ICAM-1和LFA-1在SS组的表达明显高于对照组（P〈0．01）。ICAM-1分布广泛，以导管上皮表达最强，其他腺上皮、血管内皮及淋巴细胞浸润区均有表达：LFA-1则主要表达于淋巴细胞浸润区。②ICAM-1及LFA-1在SS的表达随着淋巴细胞浸润程度的加重呈递增趋势。③ICAM-1和LFA-1呈直线相关（r=0．989，P〈0．01）。结论上皮细胞在SS中起非专职抗原提呈细胞作用，积极参与了诱导和维持淋巴细胞的浸润。     

Immunohistochemical study of the distribution of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 in chronic type B hepatitis

The expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) in the livers of 11 patients with chronic hepatitis B was studied immunohistochemically by light and electron microscopy to clarify the role of these adhesion molecules in tissue damage in chronic hepatitis B. On hepatocytes, ICAM-1 expression was confined to the bile canalicular surface when the liver inflammation was mild. In contrast, when the liver inflammation was severe, ICAM-1 was distributed on the entire surface of the hepatocyte, including the sinusoidal and lateral membranes; lymphocytes which were mostly positive for LFA-1, were often observed invading deeply among these hepatocytes. The degree of ICAM-1 expression on the hepatocytes was also related to the expression of HLA class 1 antigen. In liver showing diffuse expression of ICAM-1 on the hepatocytes, strong expression of HLA class 1 antigen was observed, and amounts of HBV in the liver were decreased. Diffuse expression of ICAM-1 and HLA class 1 antigen was mostly observed after acute exacerbation of liver inflammation. These results suggest that the ICAM-1/LFA-1 pathway is involved in the immunological mechanism, responsible for liver cell damage in chronic hepatitis B.     

乙型肝炎肝组织细胞间粘附分子-1表达

目的探讨乙型肝炎患者肝组织细胞间粘附分子－１（ｉｎｔｅｒｃｅｌｕｌａｒａｄｈｅｓｉｏｎｍｏｌｅｃｕｌｅ－１，ＩＣＡＭ－１）抗原的表达状况及其作用。方法用免疫组织化学技术检测１１例正常人和６０例乙型肝炎患者肝组织内ＩＣＡＭ－１表达情况。结果正常人和慢性无症状ＨＢｓＡｇ携带者肝细胞无ＩＣＡＭ－１表达，慢性乙型肝炎和重型肝炎患者肝细胞膜ＩＣＡＭ－１表达明显增强；肝损害越严重、坏死越明显者，其肝细胞ＩＣＡＭ－１表达越强。结论肝组织内ＩＣＡＭ－１表达在慢性乙型肝炎和重型肝炎肝坏死中起重要作用，ＩＣＡＭ－１表达水平能较好反映患者肝损害和肝组织炎症坏死程度。     

Is the intercellular adhesion molecule-1/leukocyte function associated antigen 1 pathway of leukocyte adhesion involved in the tissue damage of alcoholic hepatitis?

Alcoholic hepatitis is characterised histologically by an intense inflammatory cell infiltrate made up predominantly of neutrophils but including other cell types, particularly lymphocytes. Leukocyte cytotoxicity requires cell adhesion, which is mediated via receptors on the leukocyte surface including leukocyte function associated antigen-1 (LFA-1) which binds to the ligand intercellular adhesion molecule-1 (ICAM-1) on the target cell. The distribution of ICAM-1 and LFA-1 expression in liver biopsy specimens from patients with alcoholic liver disease was examined to ascertain whether this pathway of leukocyte adhesion is involved in the tissue damage of alcoholic hepatitis. Specimens were stained for ICAM-1 and LFA-1 by a three step immunoalkaline-phosphatase method using monoclonal antibodies against ICAM-1 and LFA-1. LFA-1 staining on portal tract inflammatory cells and parenchymal inflammatory cells and ICAM-1 staining on liver components were examined. ICAM-1 expression on hepatocytes was significantly greater in alcoholic hepatitis compared with fatty liver (p less than 0.001) and normal controls (p less than 0.01). ICAM-1 expression correlated with the histological degree of hepatocellular damage (tau = 0.79; p = 0.0005) and parenchymal inflammation (tau = 0.65; p less than 0.001, and with LFA-1 expression on parenchymal leukocytes (tau = 0.63; p = 0.01). The ICAM-1/LFA-1 pathway may therefore be involved in leukocyte mediated tissue damage during alcoholic hepatitis.     

Hepatic expression of intercellular adhesion molecule-1 (ICAM-1) in viral hepatitis B

The in situ distribution patterns of intercellular adhesion molecule-1 and human leukocyte antigen-DR antigens were studied in serial sections of 61 liver biopsy specimens from patients with hepatitis B virus infection using immunohistochemical techniques. In addition, the topographical relationship between the display of HBcAg on one hand and the expression of intercellular adhesion molecule-1 by hepatocytes on the other was analyzed with a double-staining immunohistochemical procedure in 14 selected liver biopsy samples showing chronic persistent or chronic active hepatitis and signs of active hepatitis B virus replication as reflected by the presence of variable amounts of HBcAg in a nuclear or cytoplasmic pattern of immunoreactivity. Coexpression of intercellular adhesion molecule-1 and human leukocyte antigen-DR antigens by hepatocytes correlated positively with the site and extent of the inflammatory infiltrate, which was composed of lymphocytes expressing lymphocyte function-associated antigen-1. In healthy HBsAg-positive carriers without inflammatory liver disease, no intercellular adhesion molecule-1 or human leukocyte antigen-DR expression was found on hepatocytes; in acute hepatitis, intercellular adhesion molecule-1 and human leukocyte antigen-DR were strongly expressed throughout the liver parenchyma on liver cell membranes and on sinusoidal lining cells. In chronic persistent and chronic active hepatitis and in active cirrhosis, intercellular adhesion molecule-1 and human leukocyte antigen-DR showed membranous positivity on focal clusters of hepatocytes in areas of periportal or intraacinar inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intercellular adhesion molecule-1 expression on the hepatocyte membrane of patients with chronic hepatitis B and C

ABSTRACT— The expression of intercellular adhesion molecule-1 (ICAM-1) on the hepatocyte membrane was studied in 27 patients with chronic hepatitis B and C (CHB, CHC) by immunostaining using a monoclonal antibody. ICAM-1 was expressed focally in a honeycomb-like pattern by hepatocytes in livers of 26/27 patients. The degree of ICAM-1 expression was closely related to the ALT level and the histological grade of liver damage. Abundant cytotoxic T cells (CD8 +, CD11b –) were found in ICAM-1-positive areas of the liver. Zones of focal necrosis contained both ICAM-1-positive hepatocytes and cytotoxic T cells. The expression of ICAM-1 was decreased in 4/6 CHB patients after interferon-α therapy. No relationship between the degree of hepatocyte ICAM-1 expression and viral replication markers (DNA polymerase activity and the presence of HBcAg in the liver) was observed in patients with CHB. In addition, no positive correlation was found between the distribution of ICAM-1-positive hepatocytes and HBcAg-positive hepatocytes. These results suggest that ICAM-1 may play an important role in the pathogenesis of hepatocellular injury mediated by cytotoxic T cells in CHB and CHC.     

Expression of adhesion molecules on mature cholangiocytes in canal of Hering and bile ductules in wedge biopsy samples of primary biliary cirrhosis

AIM: To examine the expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) expression on canals of Hering (CoH) and bile ductules associated with the autoimmune process of bile duct destruction in primary biliary cirrhosis (PBC). METHODS: Ten wedged liver biopsies of PBC (five cases each of stages 2 and 3) were studied. The liver specimens were processed for transmission electron microscopy. Immunohistochemistry was performed using anti-ICAM-1 and anti-LFA-1 mouse mAbs. In situ hybridization was done to examine the messenger RNA expression of ICAM-1 in formalin-fixed, paraffin-embedded sections using peptide nucleic acid probes and the catalyzed signal amplification (CSA) technique. Immunogold-silver staining for electron microscopy was performed using anti-ICAM and anti-LFA-1 mouse mAbs. The immunogold particles on epithelial cells of bile ductules and cholangiocytes of CoH cells were counted and analyzed semi-quantitatively. Western blotting was performed to confirm ICAM-1 protein expression. RESULTS: In liver tissues of PBC patients, immunohi-stochemistry showed aberrant ICAM-1 expression on the plasma membrane of epithelial cells lining bile ductules, and also on mature cholangiocytes but not on hepatocytes in CoH. LFA-1-positive lymphocytes were closely associated with epithelial cells in bile dcuctules. ICAM-1 expression at protein level was confirmed by Western blot. In situ hybridization demonstrated ICAM-1 mRNA expression in bile ductules and LFA-1 mRNA in lymphocytes infiltrating the bile ductules. By immunoelectron microscopy, ICAM-1 was demonstrated on the basal surface of epithelial cells in bile ductules and on the luminal surfaces of cholangiocytes in damaged CoH. Cells with intermediate morphology resembling progenitor cells in CoH were not labeled with ICAM-1 and LFA-1. CONCLUSION: De novo expression of ICAM-1 both on mature cholangiocytes in CoH and epithelial cells in bile ductules in PBC implies that lymphocyte-induced destruction through adhesion by ICAM-1 and binding of LFA-1-expressing activated lymphocytes takes place not only in bile ductules but also in the CoH.     

重型乙型病毒性肝炎肝内ICAM-1 mRNA表达

目的探讨细胞间粘附分子-1(ICAM-1)mRNA在重型乙型肝炎肝内的表达水平及其意义。方法用原位杂交技术检测11例正常人,5例慢性无症状HBsAg携带者(AsC)、15例慢性乙型肝炎和30例重型乙型肝炎患者肝内ICAM-1 mRNA原位表达。结果正常人和AsC肝细胞无ICAM-1 mRNA表达;重型乙型肝炎患者肝细胞ICAM-1 mRNA表达明显增强,其表达水平显著高于慢性乙型肝炎。结论ICAM-1在重型乙型肝炎肝坏死中起重要作用。     

细胞间粘附分子－1在乙型肝炎中的表达及意义

为观察细胞间粘附分子－１（ＩＣＡＭ－１）在乙型肝炎肝组织内的表达状况，探讨ＩＣＡＭ－１在乙型肝炎肝细胞免疫损伤中的作用。采用链菌素亲生物蛋白法（ＬＳＡＢ），以ＩＣＡＭ－１的单克隆抗体，检测１０４例急、慢性乙型肝炎，９例无症状携带者，１０例正常肝组织标本内ＩＣＡＭ－１抗原表达情况。结果发现：ＩＣＡＭ－１在正常肝细胞无表达，肝窦内皮细胞弱表达；ＨＢＶ感染后肝细胞呈不同程度的表达，肝窦内皮表达增强；中、重度慢性肝炎，活动性肝硬化肝细胞ＩＣＡＭ－１表达较急性肝炎，轻度慢性肝炎显著增强（Ｐ＜０．０１）；急性肝炎较轻度慢性肝炎显著增强（Ｐ＜０．０１）；轻度慢性肝炎较无症状携带者，正常肝组织显著增强（Ｐ＜０．０１）。表明ＩＣＡＭ－１在乙型肝炎肝细胞内表达与肝细胞损伤有关，对ＨＢＶ的清除可能起着重要作用，ＩＣＡＭ－１在肝窦内皮的表达有助于淋巴细胞向肝组织内浸润。