急性缺血性脑卒中患者白细胞粘附分子的表达及细胞内[Ca2+]变化的实验研究

目的探讨急性缺血性脑卒中患者外周血白细胞计数和粘附分子表达的变化,以及与中性粒细胞激活密切相关的细胞内游离钙离子浓度[Ca2+]变化,以期为脑卒中的发病机理和治疗提供有价值的理论依据.方法采用流式细胞术(FCM)检测白细胞粘附分子的表达及细胞内[Ca2+]的变化.结果脑卒中急性发作时,患者主要是中性粒细胞数增高明显,外周血白细胞CD11b、CD18的表达在发病24h内升高,同时,脑卒中患者中性粒细胞表面CD62L的表达在急性期明显降低,急性脑卒中患者中性粒细胞内[Ca2+]增加,中性粒细胞表面粘附分子CD11b、CD18的表达与细胞内[Ca2+]具有正相关性,CD62L的表达与[Ca2+]虽无明显的线性相关性,但随着[Ca2+]的增加,CD62L的表达具有下降的趋势.结论急性脑卒中发生时,白细胞被激活,粘附分子CD11b、CD18表达上调,介导白细胞与内皮细胞粘附增强,可能会加重缺血后迟发性神经元死亡的病理生理过程.同时,随着中性粒细胞的激活,细胞表面粘附分子CD62L的表达显著下调,细胞内[Ca2+]增加,在白细胞与内皮细胞的粘附过程中起重要作用.     

急性缺血性脑卒中患者白细胞粘附分子的表达及细胞内[Ca^2＋]变化的实验研究

目的 探讨急性缺血性脑卒中患者外周血白细胞计数和粘附分子表达的变化，以及与中性粒细胞激活密切相关的细胞内游离钙离子浓度[Ca^2＋]变化，以期为脑卒中的发病机理和治疗提供有价值的理论依据。方法 采用流式细胞术（FCM）检测白细胞粘附分子的表达及细胞内[Ca^2＋]的变化。结果 脑卒中急性发作时，患者主要是中性粒细胞数增高明显，外周血白细胞CD11b、CD18的表达在发病24h内升高，同时，脑卒中患者中性粒细胞表面CD62L的表达在急性期明显降低，急性脑卒中患者中性粒细胞内[Ca^2＋]增加，中性粒细胞表面粘附分子CD11b、CD18的表达与细胞内[Ca^2＋]具有正相关性，CD62L的表达与[Ca^2＋]虽无明显的线性相关性，但随着[Ca^2＋]的增加，CD62L的表达具有下降的趋势。结论 急性脑卒中发生时，白细胞被激活，粘附分子CD11b、CD18表达上调，介导白细胞与内皮细胞粘附增强，可能会加重缺血后迟发性神经元死亡的病理生理过程。同时，随着中性粒细胞的激活，细胞表面粘附分子CD62L的表达显著下调，细胞内[Ca^2＋]增加，在白细胞与内皮细胞的粘附过程中起重要作用。     

环磷酰胺和秋水仙碱联合应用对急性缺血性中风病人粘附分子的影响

目的 :探讨环磷酰胺、秋水仙碱联合应用对急性缺血性中风病人CD11a、CD11b、CD18和CD5 4的影响。方法 :84例发病 72小时内的脑梗死病人 ,随机分为处理组 (4 3例 )和对照组 (4 1)例。对照组接受急性脑梗死的基本治疗 ,处理组除接受对照组的治疗外 ,再加上环磷酰胺 0 1～ 0 2g/d静滴和秋水仙碱 1mg/d口服共 10天治疗。两组病人分别于治疗前后测CD11a、CD11b、CD18和CD5 4。结果 :处理组CD18在单核细胞、中性粒细胞上表达减少的百分率 ,以及CD5 4在单核细胞、中性粒细胞及淋巴细胞上表达减少的百分率与对照组相比 ,差异有显著性 (P <0 0 5 ) ;CD11a在单核细胞、中性粒细胞及淋巴细胞上表达减少的百分率 ,CD11b在单核细胞、中性粒细胞上表达减少的百分率两组无显著性差异 (P >0 0 5 )。结论 :环磷酰胺、秋水仙碱联合应用能减少急性缺血性中风病人白细胞上CD18、CD5 4的表达 ,对白细胞上CD11a、CD11b的表达无明显影响     

黄芪注射液对慢性阻塞性肺疾病患者黏附分子表达的影响

目的:探讨黏附分子与慢性阻塞性肺疾病(COPD)的关系及黄芪注射液在抗白细胞黏附方面的作用.方法:58例COPD患者随机分为黄芪注射液治疗组(30例)和常规治疗组(28例),健康体检者20例作为正常对照组.采用流式细胞术和酶联免疫吸附法(ELISA)测定COPD患者治疗前后及正常对照组中性粒细胞(PMN)黏附分子CD11b/CD18表达及血清中细胞间黏附分子-1(ICAM-1)水平.结果:COPD患者急性加重期和缓解期CD11b/CD18表达(86.1±9.8和76.6±8.2)和ICAM-1[(219.21±15.23)μg/L和(188.94±13.27)μg/L]均明显高于正常对照组[53.3±7.6和(132.37±16.59)μg/L,P均＜0.01].治疗后黄芪注射液治疗组CD11b/CD18表达(73.8士8.9)和ICAM-1含量[(178.32±10.46)μg/L]均显著低于正常组[分别为79.5±8.6和(196.67士11.63)μg/L,P均＜0.05].急性加重期COPD患者血清ICAM-1和CD11b/CD18表达均与PaO2、一秒钟用力呼气量(FEV1)预测值、FEV1/用力肺活量(FVC)呈负相关,与PaCO2呈正相关.结论:ICAM-1增高和CD11b/CD18表达增加参与了COPD的发生与发展,黄芪注射液具有抗白细胞黏附作用.     

粘附分子在多形核白细胞释放H2O2中的作用

目的:探讨细胞表面粘附分子在呼吸爆发时多形核白细胞(PMN)产生过氧化氢(H2O2)中的作用.方法:用氧化酚红比色法测定呼吸爆发时H2O2的产生量及CD11b、细胞闻粘附分子-1(ICAM-1)对此过程的影响.结果:细菌脂多糖(LPS)激活PMNs后,其H2O2释放量明显增加(15.03±3.50 umol·L-1比3.81±0.41 umol·L-1,P<0.005).经CD11b单抗、ICAM-1单抗、CD11b ICAM-1单抗预处理后,并未影响H2O2的释放(P>0.05).结论:在本实验条件下,CD11b、ICAM-1的表达对LPS激活的PMNs释放H2O2不是必需的.     

对一氧化碳中毒迟发性脑病相关因素的研究

目的 观察一氧化碳中毒（COP）后大鼠脑组织一氧化氮合酶（NOS）、外周血内皮细胞计数、血小板体积变化、血小板CD61表达、多形核白细胞粘附分子（CD11b/CD18)表达、海马神经细胞凋亡细胞百分比及线粒体膜电位的改变。方法 Wistar大鼠共16只随机分成正常对照组及一氧化碳中毒组各8只,制作COP动物模型,用流式细胞仪测定大鼠脑组织一氧化氮合酶（NOS）、外周血内皮细胞计数、血小板体积变化、血小板CD61表达、多形核白细胞粘附分子（CD11b/CD18)表达的动态变化,海马神经细胞凋亡细胞百分比及线粒体膜电位的改变,用分光光度法测定血浆组织型纤溶酶原激活剂（tPA)和抑制剂（PAI）。结果 COP后NOS水平降低,血小板活性增高,纤溶系统变化不明显。细胞粘附分子表达增加,线粒体膜电位降低,凋亡细胞数增加。结论 COP后血小板活必增高,细胞粘附分子表达增强,导致脑微小动物血栓形成趋势并引起白细胞浸润造成脑组织损伤,是COP迟发性脑病的重要发病因素之一。     

血管内皮细胞损伤时TLR9激活与ICAM-1、E-选择素表达的研究

目的:通过CpG ODN诱导血管内皮细胞炎症损伤,观察其TLR9 mRNA以及细胞间粘附分子-1(ICAM-1)、E-选择素表达的变化,探讨炎症反应时血管内皮损伤的可能机制。方法 :使用10μM CpG ODN(实验组)和生理盐水(对照组)分别处理正常人脐静脉血管内皮细胞(HUVEC),分别于0 h、6 h、12 h、24 h、48 h、72 h时间点,以RT-qPCR法检测TLR9 mRNA的表达,免疫细胞化学法检测ICAM-1、E-选择素表达情况。结果:TLR9 mRNA表达在实验组6 h、12 h、48 h、72 h时水平明显较对照组高(P0.05),在6h、48h表达水平明显高于其他时间组;实验组ICAM-1和E-选择素表达水平除0h时外,均明显高于对照组,其中ICAM-1在24h组时最高,E-选择素12h表达水平最高。结论:Cp G ODN损伤血管内皮细胞,激活TLR9,可呈双峰样高水平表达,且ICAM-1和E-选择素均显著升高。     

脑内注射脂多糖后常驻小胶质细胞死亡而中性粒细胞和单核细胞浸润成为主要炎症细胞

为了研究小胶质细胞和血中炎症细胞对脑炎症的影响,在正常和白细胞减少大鼠的黑质致密部(SNpc)、皮层和海马注射脂多糖(LPS),用特异标记来研究中性粒细胞、小胶质细胞和单核细胞的行为学。CD11b+和Iba-1+阳性细胞在正常脑和LPS注射后6h反应相似。注射后12hIba-1+细胞消失而CD11b+变成圆形。CD11b/Iba-1双阳性网状小胶质细胞在LPS注射后6h死亡。注射后12h检测到的CD11b+细胞是MPO+细胞。这些CD11b+/MPO+细胞在白细胞减少的大鼠脑内不出现,提示中性粒细胞浸润。MPO+中性粒细胞表达一氧化氮合酶(iNOS)、IL-1β、环氧合酶-2(COX-2)和单核细胞趋化蛋白-1(MCP-1),但在注射后18h死亡。在24h检测到的CD11b+细胞是浸润的单核细胞,因为这些细胞曾经是Iba-1+而且在白细胞减少的大鼠脑内不出现。而且,在LPS注射的脑内可以检测到移植的单核细胞。这些结果提示,在发生炎症的脑内,至少有一部分中性粒细胞和单核细胞被认为是活化的小胶质细胞。     

新生大鼠缺氧缺血性脑病时HIF-1α基因表达的变化

目的 了解新生大鼠缺氧缺血性脑病(HIE)时低氧诱导因子-1α(HIF-1α)基因表达的变化,以期寻找更为有效治疗手段.方法 24只7日龄新生SD大鼠,随机分成2组,假手术组和缺氧缺血组,根据处死时间点每组分成1 d和3 d两个小组,每组6只.缺氧缺血组结扎左颈总动脉后休息1 h,再置于8%氧浓度的低氧环境中2 h,分别于实验1 d、3 d乙醚麻醉下处死动物,留取脑组织,半数中性甲醛溶液固定,半数液氮保存,采用HE染色、逆转录聚合酶链反应(RT-PCR)和免疫组化,在蛋白和mRNA水平检测新生大鼠HIE时HIF-1α基因的表达.结果 缺氧缺血组大鼠相继表现为烦躁不安、全身发绀,呼吸加深加快、站立不稳、嗜睡、激惹或间断发作的痉挛和抽搐;HE染色显示:左侧大脑皮层出现局灶性神经元核固缩、核碎裂、核仁偏位、不清或消失、基质疏松;脑组织HIF-1αmRNA表达较对照组增加,尤其是缺氧缺血3 d组,但差异无统计学意义;免疫组化显示:缺氧缺血组1 d组和3 d组各时间点、各大鼠大脑皮层和海马区均可见不同程度的HIF-1α表达,明显高于假手术组(P=0.00),阳性表达主要在血管内皮细胞,海马和皮层的锥体细胞亦有HIF-1α阳性细胞分布.结论 新生大鼠缺氧缺血性脑病时HIF-1基因表达增强,主要表现在大脑血管内皮细胞.     

槲皮素对人急性B淋巴细胞白血病NOD/SCID小鼠细胞周期及黏附分子表达的影响

目的:探讨槲皮素对人急性B淋巴细胞白血病(B-ALL)NOD/SCID小鼠的细胞周期及黏附分子的影响。方法:对48只NOD/SCID小鼠于尾静脉注射5×106 Nalm-6细胞,建立ALL NOD/SCID小鼠模型,模型15 d后将ALL NOD/SCID小鼠随机分为3组:对照组(腹腔注射生理盐水(0.2 ml/只),环磷酰胺组(腹腔注射环磷酰胺100μg/kg)及槲皮素组(腹腔注射槲皮素3 mg/kg),治疗21 d后用流式细胞术检测Nalm-6细胞在G1、G2、M和S周期细胞百分率;计数治疗前后全血B淋巴细胞、Nalm-6细胞、中性粒细胞百分率及白细胞总数;采用双抗体夹心法测定治疗前后细胞间粘附分子-1(ICAM-1)、血管细胞粘附分子-1(VCAM-1)和P-选择素(P-selectin)蛋白表达。结果:与治疗前比较,治疗后槲皮素组ICAM-1、VCAM-1和P-selectin蛋白表达降低。血象显示,外周血中性粒细胞明显升高,而B淋巴细胞、白细胞和Nalm-6细胞明显降低; G0/G1期细胞增殖比例减少,S期和G2-M增多(P 0.05)。结论:槲皮素可能通过抑制ICAM-1蛋白表达而降低细胞间的粘附性,并将Nalm-6细胞阻滞在S期和G2-M期,对急性淋巴细胞白血病有明显的抑制作用。     

Regulation of immunoglobulin (Ig)E synthesis in the hyper-IgE syndrome

The hyper-IgE (HIE) syndrome is characterized by high IgE serum levels, chronic dermatitis, and recurrent infections. The mechanisms responsible for hyperproduction of IgE in HIE patients are presently unknown. We investigated whether spontaneous in vitro IgE synthesis by PBMC from seven HIE patients was sensitive to signals (cell adhesion, T/B cell cognate interaction and lymphokines: IL-4, IL-6, and IFN-gamma) known to regulate IgE induction in normals. Our results show that, unlike IL-4 dependent IgE synthesis induced in normals, spontaneous IgE production by PBMC from HIE patients was not blocked by monoclonal antibodies to CD2, CD4, CD3, and MHC class II antigens. Furthermore, antibodies to IL-4 and IL-6 did not significantly suppress IgE production. IFN-gamma had no significant effects on spontaneous in vitro IgE synthesis. To test whether an imbalance in lymphokine production might underlie hyperproduction of IgE in HIE patients, mitogen-induced secretion of IL-4 and IFN-gamma by PBMC was assessed. No significant difference was detected between HIE patients and normal controls. Thus, ongoing IgE synthesis in the HIE syndrome is largely independent of cell-cell interactions and endogenous lymphokines, and is due to a terminally differentiated B cell population, no longer sensitive to regulatory signals.     

血清可溶性细胞间黏附分子-1和神经元特异性烯醇化酶检测在新生儿缺氧缺血性脑病的诊断价值

目的探讨血清可溶性细胞间黏附分子-1(sICAM-1)和神经元特异性烯醇化酶(NSE)应用于新生儿缺氧缺血性脑病(HIE)的临床意义。方法双抗体夹心酶联免疫吸附法(ELISA)检测59例足月HIE患儿(HIE组,其中轻度11例,中度32例,重度16例)及30例健康足月新生儿(健康对照组)出生24 h内血清sICAM-1和NSE水平,比较各组间差异;分析HIE患儿血清sICAM-1和NSE的相关性。结果 HIE组血清sICAM-1和NSE水平高于健康对照组(P<0.05);HIE各组sICAM-1和NSE水平随HIE程度加重而增加,组间差异有统计学意义(P<0.05);HIE各组血清sICAM-1和NSE呈正相关(轻度、中度、重度组相关系数分别为0.779、0.814、0.827,P<0.05)。结论血清sICAM-1和NSE水平可作为判断HIE新生儿病情严重程度和疗效的早期指标。     

Vascular endothelium and lymphocyte adhesion molecules in minor salivary glands of patients with Sjogren's syndrome.

The aim of this study was to examine the distribution and types of adhesion molecules expressed over endothelial cells and the ligands present on lymphocytes which infiltrate exocrine glands in patients with Sjogren's syndrome. Minor salivary gland biopsies were examined from twelve patients with Sjogren's syndrome and eight normal subjects for the presence of adhesion molecules using monoclonal antibodies and an Indirect Immunoperoxidase technique. There was an increased expression of intercellular adhesion molecule-1 (ICAM-1, CD54) on endothelial cells, lymphocytes, fibroblasts and salivary gland epithelial cells. In addition we documented the expression of endothelial leukocyte adhesion molecule-1 (ELAM-1) on endothelial cells in salivary glands from patients but not the controls. Many of the endothelial cells expressing these adhesion molecules in patients with Sjogren's syndrome had the morphological appearance of high endothelial venules. V-CAM-1 was shown to be present in some of the salivary biopsies from patients with Sjogren's syndrome. Lymphocytes infiltrating salivary glands strongly express LFA-1 (CD11a/CD18) molecules. Some infiltrating lymphocytes, and most monocytes, expressed C3bi-R (CD11b/CD18) and the p150.95 (CD11c/CD18) antigens on their cell surface. The results of this study reveal the enhanced expression of vascular endothelial and lymphocyte adhesion molecules on the minor salivary glands of patients with Sjogren's syndrome. The presence of such receptors and their putative ligands indicate an important role for these molecules in the pathogenesis of Sjogren's syndrome.     

Crosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T cell adhesion.

Regulated adhesion enables T cells to migrate through tissue and transiently interact with an endless succession of cells. Monoclonal antibody (mAb) engagement of the CD3/T cell receptor (TCR) complex results in a rapid and transient augmentation of the adhesion function of LFA-1 and VLA integrin molecules on human T cells. We show in this study that mAb crosslinking of the T cell-specific accessory molecules CD7 and CD28, or treatment with the Ca2+ ionophore A23187, results in the rapid induction of integrin-mediated adhesion to three distinct ligands: the extracellular matrix protein fibronectin, and the cell surface molecules ICAM-1 and VCAM-1. Like CD3 crosslinking, increased adhesion via CD7 and CD28 crosslinking appears to involve both protein kinase C (PKC) and cAMP-dependent protein kinases. In contrast, A23187 induction of adhesion is unaffected by PKC inhibitors. CD7 is preferentially expressed on naive T cells and is unique in being a potent inducer of naive T cell adhesion. Enhanced expression/function of adhesion-inducing molecules thus overcomes relative deficits in adhesion receptor expression.     

Transmigration of blood leukocytes into the peritoneal cavity is related to the upregulation of ICAM-1 (CD54) and Mac-1 (CD11b/CD18) adhesion molecules.

BACKGROUND: Migration of blood leukocytes into the peritoneal cavity of patients treated with peritoneal dialysis appears to be an important mechanism to prevent and fight peritonitis. To study the role of adhesion molecules in the process of leukocyte transmigration, we compared the expression of several adhesion receptors between peripheral blood monocytes and macrophages isolated from overnight dwell effluents. METHODS: The study was performed in 12, stable, infection-free patients treated with continuous ambulatory peritoneal dialysis (CAPD) and in 9 patients during peritonitis. In another set of experiments, we analyzed the expression of these molecules on blood leukocytes in 10 predialysis chronic renal failure (CRF) patients and 9 healthy controls. Peritoneal cells from an 8-hour dwell were isolated by centrifugation. Expression of adhesion receptors CD11a, CD11b, CD18, CD49d, and CD54 on blood and peritoneal leukocytes was measured using flow cytometry. RESULTS: In macrophages from the uninfected effluents, expression of both subunits of Mac-1 integrin receptor (CD11b and CD18) and intercellular adhesion molecule (ICAM)-1 receptor (CD54) was upregulated compared to peripheral blood monocytes from the same patients. The median value of mean fluorescence intensity in blood and effluent was 760.3 versus 1085.8 for CD11b (p = 0.013), 288.8 versus 448.6 for CD18 (p = 0.003), and 186.1 versus 365.7 for CD54 (p = 0.001). The same adhesion receptors were also significantly upregulated on peritoneal macrophages and neutrophils during peritonitis compared to blood leukocytes. Blood leukocytes from CAPD and CRF patients showed higher expression of CD54 and CD49d molecules compared to leukocytes from healthy controls. CONCLUSIONS: These data suggest that transmigration of blood leukocytes into the peritoneal cavity during uncomplicated dialysis and in peritonitis is related to selective upregulation of ICAM-1 (CD54) and Mac-1 (CD18/CD11b) receptors.     

Circulating endothelial adhesion molecules (sE-selectin, sVCAM-1 and sICAM-1) during rHuG-CSF-stimulated stem cell mobilization

The role of leukocyte-endothelial cell interactions during granulocyte colony-stimulating factor (G-CSF)-induced stem cell mobilization is unclear. To examine endothelial activation during this process, we determined levels of circulating endothelial adhesion molecules in healthy donors undergoing G-CSF-mobilized stem cell collection. Plasma levels of soluble (s) E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were serially determined by enzyme-linked immunosorbent assays in 10 healthy donors during G-CSF-stimulated stem cell mobilization. There was a significant increase in plasma levels of all three endothelial adhesion molecules (sE-selectin, p = 0.01; sICAM-1, p = 0.003; sVCAM-1, p = 0.0002) between day 1 and day 5 of G-CSF stimulation, but only sVCAM-1 concentrations exceeded the range obtained from unstimulated controls in all stem cell donors. Increases of sCAM were accompanied by increased numbers of white blood cells and CD34(+) progenitors in peripheral blood. G-CSF-stimulated peripheral blood progenitor cells (PBPC) mobilization results in increased levels of circulating endothelial adhesion molecules that were most evident for VCAM-1 molecules. Because soluble VCAM-1 remains active in binding to the VLA-4 receptor on CD34(+) cells, it may reduce stem cell adhesiveness to endothelial cells and to bone marrow microenvironment.     

基质细胞衍生因子在多发性骨髓瘤细胞迁移和黏附中生物学作用的研究

目的研究基质细胞衍生冈子（SDF-1）存多发性骨髓瘤（MM）细胞迁移、黏附中的生物学作用以及相关信号转导.方法采用流式细胞术检测MM细胞系RPMl8226、XG-1、XG-7细胞黏附分子表达；免疫荧光技术检测SDF-1对细胞形态以及膜表而黏附分子分布的影响；通过微孔隔离实验检测SDF-1对MM细胞的趋化作用及磷脂酰肌醇3激酶（P13K）存趋化过程中的作用；免疫印迹技术检测MM细胞SDF-1对P13K的活化：结果3种MM细胞系不同程度表达多种黏附分子，RPMl8226、XG-7细胞均高表达黏附分子CD29（〉70％）、XG-1、XG-7细胞均高表达CD44（〉80％），XG-7细胞高表达CD49d（〉90％）；3种细胞系CD49e表达水平均较低（〈30％）；这些黏附分子表达水平不能被SDF-1α明显上调。SDF-1α可触发MM细胞的极化形态建立以及诱导CD29、CD49e在细胞膜的重分布。SDF-1α能促进MM细胞对内皮细胞的黏附，并能够诱导MM细胞的迁移，此作用被G蛋白抑制剂PTX及P13K抑制剂wortmannin明显抑制。结论SDF-1α促进MM细胞对内皮细胞的黏附；并触发MM细胞的极化形态建立及诱导黏附分子的重分布，从而通过P13K信号途径诱导MM细胞的迁移。     

Requirements for leukocyte adhesion molecules in nephrotoxic nephritis.

Requirements for leukocyte adhesion molecules as well as cytokines have been determined in the rat model of acute nephrotoxic nephritis. Proteinuria (at 24 h) and neutrophil accumulation in renal glomeruli (at 6 h) have been used as the endpoints. For full accumulation in glomeruli of neutrophils as well as full development of proteinuria, requirements have been demonstrated for TNF alpha, (but not IL-1), CD11b (but not CD11a), very late arising-4 (CD49d/CD29), and intercellular adhesion molecule-1 but not endothelial leukocyte adhesion molecule-1 (E-selectin). By immunohistochemical approaches, infusion of antibody to glomerular basement membrane induced glomerular upregulation of intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, and vascular adhesion molecule-1. Treatment of rats with anti-TNF alpha or soluble recombinant human TNF receptor-1 blocked this expression. Renal arterial infusion of TNF alpha induced glomerular expression of all three endothelial adhesion molecules, but infusion of IL-1 beta did not. These data suggest that, in neutrophil and complement-dependent anti-glomerular basement membrane-induced acute nephritis in rats, there are selective requirements for cytokines, beta 1 and beta 2 integrins, and endothelial adhesion molecules. These requirements contrast with those found in other vascular beds in which complement and neutrophil-induced vascular injury has been induced by deposition of immune complexes.     

同种异体手移植患者术后黏附分子的动态变化及意义

目的探讨同种异体手移植患者术后外周血黏附分子的动态变化及意义.方法用流式细胞仪对3例同种异体手移植术前患者和术后1～180 d外周血黏附分子水平进行动态观察.结果患者外周血黏附分子CD4,CD8,CD28,CD54,CD11 a的水平于术后第1天开始降低,至术后第6天为最低.术后第7天始,上述黏附分子水平逐渐回升,至180 d,CD4,CD28,CD54水平一直低于术前水平,CD11a于术后20 d回升到术前水平,而CD8则持续升高,于术后30 d,明显超过术前水平(t=4.1,P＜0.05).结论免疫抑制剂对黏附分子具有明显抑制作用.同种异体手移植术后患者无明显排斥反应与临床观察相符,提示黏附分子可作为排斥反应的监测指标,对提高移植手的存活率及其远期功能恢复具有重要意义.     

Endothelial-leukocyte adhesion molecule 1 stimulates the adhesive activity of leukocyte integrin CR3 (CD11b/CD18, Mac-1, alpha m beta 2) on human neutrophils.

Two classes of adhesion molecules have well-defined roles in the attachment of unstimulated polymorphonuclear leukocytes (PMN) to cytokine-treated endothelial cells. Endothelial-leukocyte adhesion molecule 1 (ELAM-1) on endothelial cells interacts with specific carbohydrate residues on the PMN, and the leukocyte integrins (CD18 antigens) on PMN interact with intracellular adhesion molecule 1 and other structures on endothelium. Here we show that these two classes of molecules can act sequentially in an "adhesion cascade". Interaction of PMN with ELAM-1-bearing endothelial cells causes PMN to express enhanced adhesive activity of the integrin CR3 (CD11b/CD18). Expression of ELAM-1 on the cytokine-treated endothelium appears both necessary and sufficient for the stimulation of CR3 activity since blockade of ELAM-1 with mAbs prevents the activation of CR3 by cytokine-treated endothelium, and immobilized recombinant ELAM-1 activates CR3. The ability to activate CR3 is shared by chemattractants, suggesting that ELAM-1 may serve as a "tethered chemattractant." This hypothesis is strengthened by the observation that recombinant soluble ELAM-1 directs movement of PMN in chemotaxis chambers. These results suggest a mechanism by which multiple adhesive molecules may function together in diapedesis. ELAM-1 serves both as an adhesin and as a trigger that recruits the participation of additional adhesion molecules. Our results also suggest that ligands for adhesion molecules may also be "receptors" capable of generating intracellular signals.