P-Selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice

The expression of leukocyte and endothelial cell adhesion molecules (CAMs) is essential for the emigration of leukocytes during an inflammatory response. The importance of the inflammatory response in the development of atherosclerosis is indicated by the increased expression of adhesion molecules, proinflammatory cytokines, and growth factors in lesions and lesion-prone areas and by protection in mice deficient in various aspects of the inflammatory response. We have quantitated the effect of deficiency for intercellular adhesion molecule (ICAM)-1, P-selectin, or E-selectin on atherosclerotic lesion formation at 20 wk of age in apolipoprotein (apo) E(-/-) (deficient) mice fed a normal chow diet. All mice were apo E(-/-) and CAM(+/+) or CAM(-/-) littermates, and no differences were found in body weight or cholesterol levels among the various genotypes during the study. ICAM-1(-/-) mice had significantly less lesion area than their ICAM-1(+/+) littermates: 4.08 +/- 0.70 mm(2) for -/- males vs. 5.87 +/- 0.66 mm(2) for +/+ males, and 3.95 +/- 0. 65 mm(2) for -/- females vs. 5.59 +/- 1.131 mm(2) for +/+ females, combined P < 0.0001. An even greater reduction in lesion area was observed in P-selectin(-/-) mice: 3.06 +/- 1.04 mm(2) for -/- males vs. 5.09 +/- 1.22 mm(2) for +/+ males, and 2.85 +/- 1.26 mm(2) for -/- females compared with 5.60 +/- 1.19 mm(2) for +/+ females, combined P < 0.001. The reduction in lesion area for the E-selectin null mice, although less than that seen for ICAM-1 or P-selectin, was still significant (4.54 +/- 2.14 mm(2) for -/- males vs. 5.92 +/- 0.63 mm(2) for +/+ males, and 4.38 +/- 0.85 mm(2) for -/- females compared with 5.94 +/- 1.44 mm(2) for +/+ females, combined P < 0.01). These results, coupled with the closely controlled genetics of this study, indicate that reductions in the expression of P-selectin, ICAM-1, or E-selectin provide direct protection from atherosclerotic lesion formation in this model.     

Infection of human intestinal epithelial cells with invasive bacteria upregulates apical intercellular adhesion molecule-1 (ICAM)-1) expression and neutrophil adhesion.

The acute host response to gastrointestinal infection with invasive bacteria is characterized by an accumulation of neutrophils in the lamina propria, and neutrophil transmigration to the luminal side of the crypts. Intestinal epithelial cells play an important role in the recruitment of inflammatory cells to the site of infection through the secretion of chemokines. However, little is known regarding the expression, by epithelial cells, of molecules that are involved in interactions between the epithelium and neutrophils following bacterial invasion. We report herein that expression of ICAM-1 on human colon epithelial cell lines, and on human enterocytes in an in vivo model system, is upregulated following infection with invasive bacteria. Increased ICAM-1 expression in the early period (4-9 h) after infection appeared to result mainly from a direct interaction between invaded bacteria and host epithelial cells since it co-localized to cells invaded by bacteria, and the release of soluble factors by epithelial cells played only a minor role in mediating increased ICAM-1 expression. Furthermore, ICAM-1 was expressed on the apical side of polarized intestinal epithelial cells, and increased expression was accompanied by increased neutrophil adhesion to these cells. ICAM-1 expression by intestinal epithelial cells following infection with invasive bacteria may function to maintain neutrophils that have transmigrated through the epithelium in close contact with the intestinal epithelium, thereby reducing further invasion of the mucosa by invading pathogens.     

Characterization of the function of intercellular adhesion molecule (ICAM)-3 and comparison with ICAM-1 and ICAM-2 in immune responses

We have characterized the immunobiology of the interaction of intercellular adhesion molecule 3 (ICAM-3; CD50) with its counter- receptor, leukocyte function-associated antigen 1 (LFA-1; CD11a/CD18). Purified ICAM-3 supported LFA-1-dependent adhesion in a temperature- and cation-dependent manner. Activation of cells bearing LFA-1 increased adhesiveness for ICAM-3 in parallel to adhesiveness for ICAM- 1. Although CBR-IC3/1 monoclonal antibody (mAb) blocked adhesion of cells to purified LFA-1, when tested alone, neither CBR-IC3/1 nor five novel ICAM-3 mAbs characterized here blocked adhesion of cells to purified ICAM-3 or homotypic adhesion. Two ICAM-3 mAbs, CBR-IC3/1 and CBR-IC3/2, were required to block LFA-1-dependent adhesion to purified ICAM-3- or LFA-1-dependent, ICAM-1-, ICAM-2-independent homotypic adhesion of lymphoid cell lines. Two ICAM-3 mAbs, CBR-IC3/1 and CBR- IC3/6, induced LFA-1-independent aggregation that was temperature and divalent cation dependent and was completely inhibited by ICAM-3 mAb, CBR-IC3/2, recognizing a distinct epitope. Purified ICAM-3 provided a costimulatory signal for proliferation of resting T lymphocytes. mAb to ICAM-3, together with mAbs to ICAM-1 and ICAM-2, inhibited peripheral blood lymphocyte proliferation in response to phytohemagglutinin, allogeneic stimulator cells, and specific antigen. Inhibition was almost complete and to the same level as with mAb to LFA-1, suggesting the most functionally important, and possibly all, of the ligands for LFA-1 have been defined.     

亚低温处理脑缺血再灌注损伤后细胞间黏附分子-1的表达变化

目的观察亚低温处理大鼠脑缺血再灌注损伤后缺血侧脑组织细胞间黏附分子-1(intercellularadhesionmolecule-1,ICAM-1)的表达变化,探讨与损伤神经细胞凋亡的关系。方法采用大鼠局灶性脑缺血再灌注损伤模型,大脑中动脉阻塞2h,再灌注损伤12h,用原位缺口末端标记(TUNEL)法、反转录聚合酶链反应(RT-PCR)技术和斑点印迹杂交(Dotblotting)法分别检测假手术组、对照组和亚低温组缺血侧脑组织凋亡细胞百分率、ICAM-1mRNA和ICAM-1蛋白表达水平。结果对照组缺血侧脑组织ICAM-1mRNA、ICAM-1蛋白表达水平和凋亡细胞百分率明显高于假手术组;亚低温组缺血侧脑组织ICAM-1mRNA、ICAM-1蛋白表达水平和凋亡细胞百分率较对照组明显降低。结论亚低温的抗脑缺血再灌注损伤后损伤神经细胞凋亡作用可能与其下调缺血侧脑组织ICAM-1表达有关。     

大鼠骨髓间充质干细胞血管细胞黏附分子1及细胞间黏附分子1的表达(英文)

背景:骨髓间充质干细胞系统性输注后,何种因素促使其迁移到正确部位尤为关键,目前认为黏附分子在介导骨髓间充质干细胞向缺血或损伤组织迁移过程中起重要作用.目的:观察血管细胞黏附分子1与细胞间黏附分子1在大鼠骨髓间充质干细胞中的表达.方法:采用直接贴壁法体外分离培养大鼠骨髓间充质干细胞,免疫细胞化学染色检测血管细胞黏附分子1及细胞间黏附分子1蛋白的表达,应用免疫荧光直标法在流式细胞仪上检测血管细胞黏附分子1及细胞间黏附分子1抗原的表达率,RT-PCR半定量分析血管细胞黏附分子1及细胞间黏附分子1 mRNA的表达.结果与结论:免疫细胞化学染色结果显示,骨髓间充质干细胞血管细胞黏附分子1呈弱阳性表达,细胞间黏附分子1呈强阳性表达.流式细胞仪检测结果显示,血管细胞黏附分子1表达率为6%,细胞间黏附分子1表达率为100%.RT-PCR检测结果显示,血管细胞黏附分子1 mRNA呈微弱表达,细胞间黏附分子1 mRNA呈高度表达.提示在生理状态下,体外培养的大鼠骨髓间充质干细胞低表达血管细胞黏附分子1,高表达细胞间黏附分子1.     

神经细胞黏附分子L1-Ig(1-4)的原核表达及其功能

目的:利用基因克隆、表达、纯化等分子生物学手段获取具有生物活性的神经细胞黏附分子L1(L1)的Ig(1-4)结构域融合蛋白。方法:实验于2001-10/2004-12在解放军第二军医大学神经生物教研室完成。①从新生4d的SD大鼠的海马组织中提取总RNA,采用反转录-聚合酶链反应法获取L1-Ig(1-4)基因,进行序列分析后构建表达载体pET28a( )-L1-Ig(1-4)。②转染大肠杆菌BL21,用IPTG诱导L1-Ig(1-4)的表达。③利用Ni2 -NTA柱纯化和复性。④用L1-Ig(1-4)融合蛋白观察培养脊髓原代神经元轴突生长情况及其活性,未加入融合蛋白的细胞做对照。结果:①克隆出编码正确的大鼠L1-Ig(1-4)基因。②并在大肠杆菌中获得高效表达,表达产物占全菌总蛋白的28.3%。③Ni2 -NTA柱纯化后的纯度达90%以上。④加入融合蛋白后脊髓神经元突触的生长能力较未加入融合蛋白的细胞增强犤(56±3.8),(43±2.7)μm,P<0.01犦。结论:通过原核表达可大量获得L1-Ig(1-4)融合蛋白,该融合蛋白同样具有促神经生长的生物学活性。     

In vivo MR imaging of intercellular adhesion molecule‐1 expression in an animal model of multiple sclerosis

Upregulation of intercellular adhesion molecule 1 (ICAM‐1) is an early event in lesion formation in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Monitoring its expression may provide a biomarker for early disease activity and allow validation of anti‐inflammatory interventions. Our objective was therefore to explore whether ICAM‐1 expression can be visualized in vivo during EAE with magnetic resonance imaging (MRI) using micron‐sized particles of iron oxide (MPIO), and to compare accumulation profiles of targeted and untargeted MPIO, and a gadolinium‐containing agent. Targeted αICAM‐1‐MPIO/untargeted IgG‐MPIO were injected at two model‐characteristic phases of EAE (in myelin oligodendrocyte glycoprotein_35–55‐immunized C57BL/6 J mice), that is, at the peak of the acute phase (14 ± 1 days post‐immunization) and during the chronic phase (26 ± 1 days post‐immunization), followed by T₂*‐weighted MRI. Blood–brain barrier (BBB) permeability was measured using gadobutrol‐enhanced MRI. Cerebellar microvessels were analyzed for ICAM‐1 mRNA expression using quantitative PCR (qPCR). ICAM‐1 and iron oxide presence was examined with immunohistochemistry (IHC). During EAE, ICAM‐1 was expressed by brain endothelial cells, macrophages and T‐cells as shown with qPCR and (fluorescent) IHC. EAE animals injected with αICAM‐1‐MPIO showed MRI hypointensities, particularly in the subarachnoid space. αICAM‐1‐MPIO presence did not differ between the phases of EAE and was not associated with BBB dysfunction. αICAM‐1‐MPIO were associated with endothelial cells or cells located at the luminal side of blood vessels. In conclusion, ICAM‐1 expression can be visualized with in vivo molecular MRI during EAE, and provides an early tracer of disease activity. Copyright © 2014 John Wiley & Sons, Ltd.     

山莨菪碱和己酮可可碱对内毒素诱导大鼠心肌组织细胞间黏附分子-1的抑制作用

目的研究山莨菪碱（654—2）和己酮可可碱（PTX）对内毒素诱导大鼠心肌组织细胞间黏附分子-1（ICAM-1）的抑制作用。方法将健康Wistar大鼠按随机数字表法分为对照组、模型组、654—2组、PTX组和654—2＋PTX组，每组各时间点6只。经尾静脉注射脂多糖（LPS）5mg／kg制备动物模型。于术后0、2、4、6、8和10h不同时间点分别处死大鼠取心肌组织，采用蛋白质免疫印迹法（Western blotting）检测心肌组织ICAM-1蛋白的表达。结果注射LPS6h时大鼠心肌组织ICAM-1蛋白的表达明显升高（P〈0．01），随后ICAM-1蛋白的表达逐渐下降，至10h时仍有表达（P〈0．05）。654—2及PTX干预后均可减少心肌组织ICAM-1蛋白的表达（P均〈O．01），且654—2与PTX联合使用可使心肌组织ICAM-1蛋白的表达减少更显著，与单用654—2和PTX比较差异均有统计学意义（P均〈0．05）。结论654—2和PTX联合使用可明显抑制内毒素诱导的大鼠心肌组织ICAM-1蛋白的表达，从而起到对心肌组织的保护作用。     

Carcinoembryonic antigen-related cell adhesion molecule 1 modulates vascular remodeling in vitro and in vivo

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a cellular adhesion molecule of the Ig superfamily, is associated with early stages of angiogenesis. In vitro, CEACAM1 regulates proliferation, migration, and differentiation of murine endothelial cells. To prove that CEACAM1 is functionally involved in the regulation of vascular remodeling in vivo, we analyzed 2 different genetic models: in Ceacam1-/- mice, the Ceacam1 gene was deleted systemically, and in CEACAM1(endo+) mice, CEACAM1 was overexpressed under the control of the endothelial cell-specific promoter of the Tie2 receptor tyrosine kinase. In Matrigel plug assays, Ceacam1-/- mice failed to establish new capillaries whereas in CEACAM1(endo+) mice the implants were vascularized extensively. After induction of hind limb ischemia by femoral artery ligation, Ceacam1-/- mice showed significantly reduced growth of arterioles and collateral blood flow compared with their WT littermates. In agreement with a causal role of CEACAM1 in vascular remodeling, CEACAM1(endo+) mice exhibited an increase in revascularization and collateral blood flow after arterial occlusion. Our findings indicate that CEACAM1 expression is important for the establishment of newly formed vessels in vivo. Hence CEACAM1 could be a future target for therapeutic manipulation of angiogenesis in disease.     

外周血细胞间黏附因子1水平与Graves病的相关性

目的：Graves病被认为是一种淋巴细胞介导的自身免疫性疾病，细胞间黏附因子1在白细胞由血液至炎症部位的趋化及免疫介导细胞信号传导中起重要作用。探讨细胞间黏附因子1与Graves病的相关性。 方法：①对象：为202例中国北方汉族人，其中2004—02／12青岛市中心医院内分泌科住院或门诊初诊未治疗Graves病患者139例，同期体检健康成人63人。②分组：按Graves病发病年龄分为早发Graves病组（发病年龄〈40岁）78例和晚发Graves病组（发病年龄≥40岁）61例；健康对照组63例。所有受试者对检测项目知情同意。正常对照组与Graves病组的年龄、性别构成比差异均无显著性。③方法及评估：运用酶联免疫吸附法技术，检、删各组血清游离T3，游离T4，促甲状腺素，促甲状腺素受体抗体，甲状腺球蛋白抗体，甲状腺过氧化物酶抗体，细胞间黏附因子1水平变化。 结果：①与正常对照组比较，Graves病组游离T3，游离T4，超敏促甲状腺素，促甲状腺素受体抗体，甲状腺过氧化物酶抗体，甲状腺球蛋白抗体差异均有显著性（P〈0．05）。②早发Graves病组和晚发Graves病组的游离T3，游离T4，超敏促甲状腺素，促甲状腺素受体抗体，甲状腺过氧化物酶抗体，甲状腺球蛋白抗体差异均无显著性（P〉0．05）。③Graves病组血清细胞间黏附因子1的水平高于正常对照组（P〈0．05）；晚发Graves病组血清细胞间黏附因子1的水平高于早发Graves病组（P〈0．05）。 结论：Graves病患者外周血中细胞间黏附因子1水平增高：且晚发患者更明显。     

Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon gamma and is mediated by intercellular adhesion molecule 1 (ICAM-1)

The cell surface expression and function of the LFA-1 ligand, intercellular adhesion molecule 1 (ICAM-1), on epidermal keratinocytes (EK) was studied. ICAM-1 expression on the surface of cultured EK was either absent or weak, but was induced by treating EK with rIFN-gamma or TNF for 4-48 h. IFN-gamma and TNF were synergistic. IFN-gamma treatment increased T lymphoblast adhesion from less than 2% to 20-40%, with a concentration dependence similar to that seen for ICAM-1 induction. All of the adhesion to EK was inhibited by LFA-1 and ICAM-1 mAbs, but not by HLA-DR, CD2, or LFA-3 mAbs. There was no difference in the level of T lymphoblast adhesion to IFN-gamma-treated allogeneic or autologous EK. ICAM-1 purified from the HeLa epithelioid cell line and reconstituted into planar membranes also supported efficient adhesion of T lymphoblasts that was blocked by LFA-1 mAb bound to the T lymphoblasts or ICAM-1 mAb bound to the planar membranes. T lymphoblasts adherent to EK or ICAM-1 planar membranes were isolated by panning, and surface markers were analyzed by immunofluorescence flow cytometry. The adherent T cells were a phenotypically skewed subpopulation. They were enriched for CD8+ cells and expressed 1.5-2.5-fold higher LFA-1 and CD2 compared with the unseparated population.     

In vitro studies of the antirhinovirus activity of soluble intercellular adhesion molecule-1.

We studied the in vitro antirhinovirus activity of a soluble form of intercellular adhesion molecule-1 (sICAM-1). sICAM-1 inhibited the cytopathic effect of 10 representative human rhinovirus (HRV) serotypes of the major receptor group with, 50% effective concentrations (EC50s) of 0.1 to 7.9 micrograms/ml. Cell type-dependent variation in the inhibitory activity of sICAM-1 was observed for two major receptor group serotypes in HeLa cells (EC50, greater than 32 micrograms/ml), and no inhibitory effect was observed for two serotypes which use different cell receptors. Yield reduction assays showed that sICAM-1 inhibited the replication of HRV serotype 39 (HRV-39) in human adenoid explants in a concentration-dependent manner. No direct inactivation of infectivity of HRV-39 (EC50, 0.5 microgram/ml) was observed after incubation with sICAM-1 (32 micrograms/ml) for up to 24 h. Single-cycle-of-replication experiments with the addition of sICAM-1 at 10 micrograms/ml at different times showed that the inhibitory effect occurs only when sICAM-1 is added within 30 min after infection. In experiments in which absorption was carried out at 4 degrees C and then a single cycle of replication incubation was carried out at 33 degrees C, it was found that sICAM-1 at 10 micrograms/ml was inhibitory only when it was present during the absorption period. Our data show that sICAM-1 is inhibitory for representative major receptor group serotypes of HRV in two cell lines and human respiratory epithelium, that the interaction of sICAM-1 with HRV is readily reversible by dilution, and that the inhibitory effect of sICAM-1 on virus replication is present early in the infection cycle.     

粘附分子和白介素8在早期急性呼吸窘迫综合征中的作用研究

目的 :探讨急性失血致低血容量性休克后低剂量内毒素动物模型中血浆白介素 8(IL 8)、细胞间粘附分子 1(ICAM 1)、血管内皮粘附分子 1(VCAM 1)水平的改变及其与血浆 IL 1β水平的关系。方法 :2 2只新西兰白兔随机分成 4组 :1低血容量性休克组 (休克组 ,6只 ) :急性失血持续 1小时 ,以心排血量低于基础值 40 %为准 ,休克恢复 6 0分钟后再观察 4小时 ;2内毒素 (L PS)组 (6只 ) :以 1.0 0～ 1.2 5μg/ kg L PS静注 ;3休克 L PS组 (6只 ) :低血容量性休克恢复 6 0分钟后再静注低剂量 L PS;4正常对照组 (4只 )。分别在休克前、休克 6 0分钟、休克恢复 6 0分钟、静注 L PS2和 4小时 5个点抽血测 IL 8、IL 1β、ICAM 1和 VCAM 1水平。结果 :休克 L PS组血浆 VCAM 1水平于注射 L PS4小时后显著高于正常对照组 (P<0 .0 5 ) ;血浆ICAM 1水平于注射内毒素第 2和 4小时后亦均高于正常对照组 (P均 <0 .0 5 ) ;休克组、休克 L PS组血浆IL 8浓度在注射 L PS后 2小时均显著高于正常对照组 (P均 <0 .0 5 ) ;休克组和休克 L PS组兔在休克期血浆 IL 1β浓度显著升高 ,而休克 L PS组于静注 1μg/ kg L PS后 2和 4小时 ,血浆 IL 1β浓度再次显著升高。结论 :低血容量性休克后再注射低剂量内毒素可导致血浆 ICAM 1和     

肿瘤组织中细胞间粘附分子-1表达的PET/近红外荧光跨模态靶向成像表征

目的验证基于双标记细胞间粘附分子-1（ICAM-1）单抗示踪剂,进行胰腺癌组织中ICAM-1的正电子发射断层（PET）/近红外荧光（NIRF）跨模态靶向成像的可行性。方法采用流式细胞术测定2种胰腺癌细胞系BxPC-3、MIA PaCa的ICAM-1表达水平。通过生物耦联和配位反应制备NIRF荧光团和[89Z]锆核素双标记示踪剂。在上述细胞系构建的裸鼠皮下移植瘤模型（简称模型鼠）中,测试示踪剂的特异性、跨模态成像性能和生物分布特性;尝试在BxPC-3模型鼠中进行解剖前/后离体组织器官NIRF光学成像。最后采用组织病理学方法确认ICAM-1在移植瘤组织中的分布。结果BxPC-3与MIA PaCa细胞系的ICAM-1表达水平有显著差异（P < 0.05）。PET/NIRF跨模态成像和放射性生物分布实验显示,在2种模型鼠中,肿瘤的示踪剂摄取峰值的差异也有统计学意义（P < 0.05）。PET/NIRF成像所显示的肿瘤位置相互吻合。解剖切除瘤体前后,荧光信号随瘤体转移,周围组织几乎无残留信号。免疫组织化学染色显示,这2种移植瘤组织的ICAM-1表达水平差异与其示踪剂浓聚水平差异正相关（P < 0.05）。结论本研究确认了以ICAM-1为靶标的双标记单抗示踪剂,用于胰腺癌组织临床前靶向跨模态成像是可行的,这为同时实现肿瘤活体全身成像和肿瘤组织原位可视化提供了例证,揭示了基于ICAM-1靶向成像的病灶检测、手术导航等临床转化应用的潜力。     

P选择素单克隆抗体对大鼠肝缺血—再灌注损伤的治疗作用研究

目的：探讨Ｐ选择素单克隆抗体（单抗）对大鼠肝缺血再灌注损伤的保护作用。方法：在肝缺血再灌注大鼠模型上观察了细胞间粘附分子１和Ｐ选择素的变化，并用Ｐ选择素单抗对其进行阻断治疗。结果：缺血再灌注大鼠肝细胞发生水肿及空泡变性，血清天冬氨酸转氨酶和丙氨酸转氨酶水平升高；但再灌注前５分钟经静脉注射Ｐ选择素单抗，则肝组织与正常组相近，肝细胞未见空泡变性，血清酶水平明显减低；酶联免疫吸附试验发现，再灌注后血清ＩＣＡＭ１和血浆Ｐ选择素水平显著升高，经Ｐ选择素单抗处理的大鼠血ＩＣＡＭ１和Ｐ选择素明显下降。结论：ＩＣＡＭ１和Ｐ选择素与缺血再灌注损伤密切相关，Ｐ选择素单抗对肝缺血再灌注损伤具有保护作用。     

Elevated serum levels of intercellular adhesion molecule ICAM-1 in Pseudoxanthoma elasticum

BACKGROUND: Pseudoxanthoma elasticum (PXE, OMIM 177850 and 264800) is a rare heritable disorder predominantly affecting the skin, the eyes and the vascular system. The disease is caused by mutations in the ABCC6 gene and is characterized by calcification and extracellular matrix remodeling, including alterations of the vessel walls. Here, we investigated the cell adhesion molecules ICAM-1 in PXE patients. METHODS: Soluble ICAM-1 was determined in 58 non-consanguineous PXE patients by quantitative sandwich enzyme immunoassay. The allelic frequencies of the ICAM-1 variant p.K469E were analyzed in patients and age- and sex-matched controls. RESULTS: Soluble ICAM-1 levels were significantly elevated in male and female PXE patients (p<0.02 and p<0.001, respectively). In addition, the ICAM-1 concentration correlated with the ABCC6 gene status of the PXE patients. The ICAM variant p.K469E genotypes were not different in PXE patients and age- and sex-matched controls. CONCLUSIONS: Our data show for the first time increased ICAM-1 concentrations in PXE patients, potentially due to the chronic oxidative stress and elevated protease activity followed by extracellular matrix remodeling which have been previously observed in PXE patients.     

眼针治疗急性脑缺血再灌注损伤大鼠海马组织细胞间黏附因子1的变化

背景：病理情况下,细胞间黏附因子1表达明显升高,促进炎症反应的发生,加重脑组织损伤。目的：观察眼针穴区、穴区外治疗对急性脑缺血再灌注损伤模型大鼠海马组织细胞间黏附因子1表达的影响。方法：40只SD大鼠随机等分为正常组、假手术组、模型组、眼针穴区组和穴区外组。后3组用线栓法复制脑缺血再灌注损伤大鼠模型,栓塞线插入深度1．8-2．2cm,眼针组于脑缺血再灌注即刻及取材前30min,取肝区、上焦区、下焦区、肾区平刺眼眶周治疗20min。穴区外组选择眼针同名穴区的外3mm处为针刺部位,刺法与眼针穴区相同。结果与结论：眼针穴区治疗后大鼠神经功能缺损评分下降,海马组织细胞间黏附因子1蛋白及mRNA表达显著降低（P〈0．01）。穴区外组治疗后大鼠神经功能缺损评分及海马组织细胞间黏附因子1蛋白及mRNA表达无明显变化。提示眼针具有明显的改善大鼠脑缺血再灌注损伤的作用,其机制与下调海马组织细胞间黏附因子表达有关。     

Longitudinal analysis of soluble intercellular adhesion molecule 1 in retinal vasculitis patients

Abstract. Increased levels of soluble intercellular adhesion molecule 1 (sICAM-1) in serum have been demonstrated in several human disease conditions. We have previously shown, in a point-prevalence study, a positive correlation between sICAM-1 levels and disease relapse in patients with idiopathic retinal vasculitis. We now report a longitudinal study over 1 year in which sICAM-1 levels were compared with clinical disease status in order to determine this relationship further. Serum samples from 11 patients with idiopathic retinal vasculitis were tested for the presence of sICAM-1 by enzyme linked immunosorbent assay. Eight control subjects were also tested. Five out of 11 patients presented with relapse and had raised sICAM-1 levels compared with quiescent periods of their disease. Five out of 11 patients showed no relapse over 1 year and also no increase in sICAM-1 levels. One patient showed increased levels of sICAM-1, but no clinical signs of relapse. These results indicate that sICAM-1 is associated with disease activity in retinal vasculitis patients and could indicate dysfunction of the blood-retina barrier.     

恶性淋巴增殖性疾病患者血清可溶性细胞间粘附分子-1的检测

目的观察恶性淋巴细胞增殖性疾病患者血清可溶性细胞间粘附分子１（ｓＩＣＡＭ１）水平的变化及其与病情、疗效的关系。方法采用亲合素和生物素标记的酶联免疫法,对多发性骨髓瘤（ＭＭ）、恶性淋巴瘤（ＭＬ）及急性淋巴细胞白血病（ＡＬＬ）患者化疗前后血清ｓＩＣＡＭ１水平进行检测。结果２２例ＭＭ患者中９例（４１％）、３２例非霍奇金淋巴瘤（ＮＨＬ）患者中１７例（５３％）、１９例ＡＬＬ患者中１２例（６３％）的血清ｓＩＣＡＭ１水平高于正常。血清ｓＩＣＡＭ１水平,ＭＭ患者中受Ｃ反应蛋白和β２微球蛋白为依据的Ｂａｔａｉｌｅ分期的影响,与Ｄｕｒｉｅ分期无关;ＮＨＬ患者中,与病理类型、ＡｎｎＡｒｂｏｒ分期、Ｂ症状有关,与血清乳酸脱氢酶无关;ＡＬＬ患者中,合并中枢神经系统白血病者明显高于未合并者。血清ｓＩＣＡＭ１升高者与血清ｓＩＣＡＭ１正常者比较,前者疗效较差。动态观察发现,随着病情缓解,血清ｓＩＣＡＭ１水平亦降至正常。结论血清ｓＩＣＡＭ１水平的检测有助于判断患者的病情及疗效。     

Modulation of soluble phases of endothelial/leukocyte adhesion molecule 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 with interleukin-1beta after experimental endotoxic challenge

OBJECTIVE: To evaluate the effect of treatment with interleukin 1beta (IL-1beta) on the concentrations of soluble adhesion molecules after an endotoxic challenge. DESIGN: Randomized, controlled study. SETTING: Experimental Unit, Virgen de las Nieves University Hospital. SUBJECTS: Seventy-two female CBA/H mice of 20 to 21 g, supplied by the animal center of the Experimental Unit. INTERVENTION: The mice were randomized into three groups of 24. Group 1 (sham) received two intraperitoneal (ip) doses of 0.1 mL of phosphate-buffered saline; group 2 (lipopolysaccharide) was injected with 125 mg/kg lipopolysaccharide (Escherichia coli) (i.p.) 24 hrs after 0.1 mL of phosphate-buffered saline; group 3 was pretreated with 80 ng (i.p.) of IL-1beta per mouse 24 hrs before the endotoxic challenge. MEASUREMENTS AND MAIN RESULTS: At 1, 2, 4, and 24 hrs after the endotoxic challenge, the concentrations of soluble endothelial/leukocyte adhesion molecule 1 (ELAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured in the three groups. There was a significant increase (p <.01) in these concentrations at these times in comparison with the sham group. The use of IL-1beta produced a significant decrease (p <.05) in the three molecules among the treated group versus the group submitted only to the challenge; concentrations of ELAM-1 significantly decreased to below those of the sham group, and those of VCAM-1 reduced to levels that did not significantly differ from those of the sham group. CONCLUSION: Endotoxin administration significantly increases the concentrations of soluble ELAM-1, ICAM-1, and VCAM-1 in mice. Treatment with IL-1beta significantly decreases these concentrations, probably attenuating cell injury and organ dysfunction.