火把花根片对急性肺损伤的保护作用研究

目的：探讨中药火把花根片对油酸诱导大鼠急性肺损伤（ALI）的保护作用。方法：36只Wistar大鼠被随机分为3组,采用尾静脉注射油酸建立ALI模型。火把花根组于注射油酸前用火把花根溶液连续灌胃10d,每日2次;正常对照组尾静脉注射0.04 ml/kg生理盐水。各组均于注射油酸后即刻（0）、0.5、1、2、3和4 h后取血测定中性粒细胞（PMN）表面黏附分子CD11a、CD11b、CD18阳性表达率和中性粒细胞弹性蛋白酶（NE）活性;术毕活杀动物,观察肺组织湿/干重比（W/D）、肺通透指数（LPI）和肺损伤评分（LIS）变化以及支气管肺泡灌洗液（BALF）中活化PMN百分比,并进行肺组织病理学光镜观察。结果：与正常对照组比较,ALI组外周血PMN黏附分子CD11a、CD11b、CD18阳性表达率、血清NE活性以及肺组织W/D、LPI、LIS和BALF中PMN百分比均显著升高;与ALI组比较,火把花根组肺W/D、LPI、LIS及BALF中PMN百分比均明显降低,损伤0.5 h以后各时间点PMN表面CD11a、CD11b、CD18表达和NE活性均显著降低（P均〈0.01）。光镜下观察火把花根组肺组织损伤程度较ALI组明显减轻。结论：火把花根片对油酸诱导ALI有一定保护作用,其作用机制可能与抑制PMN表面CD11a、CD11b和CD18表达及NE释放有关。     

丹参注射液对慢性阻塞性肺疾病外周血白细胞黏附分子CD11b表达的影响

目的：研究外周血白细胞黏附分子CD11b与慢性阻塞性肺疾病（COPD）发病的关系及丹参注射液对CD11b表达及肺功能的影响。方法：采用全血直接免疫荧光流式细胞术检测我院81例COPD急性发作期患者（COPD组．分为常规治疗组和丹参治疗组）和21例正常对照组外周血白细胞黏附分子CD11b的表达及其相应的肺功能（FEV1）。结果：（1）COPD组患者CD11b水平明显高于正常对照组（P〈0．01），二者肺功能差异亦有显著性（P〈0．01）。（2）常规治疗组和丹参治疗组治疗后CD11b差异有显著性（P〈0．05），二者治疗后肺功能差异亦有显著性（P〈0．05）。（3）COPD组白细胞黏附分子CD11b与肺功能呈显著负相关（治疗前r=-0．536，P〈0．01：常规治疗组治疗后r=-0．634，P〈0．01；丹参治疗组治疗后r=-0．738．P〈0．01）。结论：CD11b参与了COPD的发病。丹参明显阻抑外周血CD11b的表达．这可能是此类中药具有抗炎活性的机制之一。[著者文摘]     

丹参注射液对慢性阻塞性肺疾病外周血白细胞黏附分子CD11b表达的影响

目的:研究外周血白细胞黏附分子CD11b与慢性阻塞性肺疾病(COPD)发病的关系及丹参注射液对CD11b表达及肺功能的影响。方法:采用全血直接免疫荧光流式细胞术检测我院81例COPD急性发作期患者(COPD组,分为常规治疗组和丹参治疗组)和21例正常对照组外周血白细胞黏附分子CD11b的表达及其相应的肺功能(FEV1)。结果:(1)COPD组患者CD11b水平明显高于正常对照组(P<0.01),二者肺功能差异亦有显著性(P<0.01)。(2)常规治疗组和丹参治疗组治疗后CD11b差异有显著性(P<0.05),二者治疗后肺功能差异亦有显著性(P<0.05)。(3)COPD组白细胞黏附分子CD11b与肺功能呈显著负相关(治疗前r=-0.536,P<0.01;常规治疗组治疗后r=-0.634,P<0.01;丹参治疗组治疗后r=-0.738,P<0.01)。结论:CD11b参与了COPD的发病,丹参明显阻抑外周血CD11b的表达,这可能是此类中药具有抗炎活性的机制之一。     

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.     

肺部感染患者外周血中性粒细胞黏附分子CD11b CD18髓过氧化物酶的变化及临床意义

目的了解肺部感染患者外周血中性粒细胞功能即表达黏附分子CD11b、CD18、髓过氧化物酶（MPO）的变化及临床意义。方法应用流式细胞舣检测30例普通肺部感染患者治疗前后、18例重症肺部感染患者治疗前外周血中性粒细胞表面表达黏附分子CD11b、CD18、MPO的变化，并与25例健康人进行比较。结果①普通组和重症组患者外周血中性粒细胞黏附分子CD11b、CD18表达明显高于正常对照组，有统计学意义（P＜0．05或P＜0．01）；普通组MPO表达明显高于正常对照组和重症肺炎组，有统计学意义（P＜0．01）；重症组MPO明显低于普通组，有统计学意义（P＜0．01）。②普通组常规治疗10d后CD11b、CD18与治疗前相比变化不明显（P＞0，05）；治疗10d后普通组MPO表达较治疗前明显降低，有统计学意义（P＜0．01）；殆疗后各组数据均较治疗前有所降低，但仍未降至正常对照组水平，有统计学意义。结论肺部感染患者外周血中性粒细胞处于活化状态，表达黏附分子CD11b、CD18增多；中性粒细胞杀菌功能增强，表现为MPO表达增多；重症肺部感染可抑制MPO表达，从而影响中性粒细胞的杀菌功能，对患者预后不利。     

丹参酮对脑梗死患者白细胞表面黏附分子表达的影响

目的:通过对白细胞表面黏附分子表达的分析,探讨丹参酮治疗急性脑梗死的作用机制。方法:采用双盲随机对照方法将80例急性脑梗死患者分为两组,治疗组给予丹参酮注射液2 m l,对照组给予注射用水,两组分别溶于生理盐水250 m l静脉滴注,每日1次,连用7 d。两组于治疗前后取外周血分离多形核白细胞(PM N),应用间接免疫荧光标记,流式细胞仪检测白细胞表面黏附分子CD 11a、CD 18、CD 18/CD 11a(LFA 1)免疫阳性细胞数;应用透射电镜观察外周血PM N超微结构变化。结果:丹参酮能明显降低外周血白细胞表面黏附分子CD 11a、CD 18、LFA 1免疫阳性细胞数;PM N超微结构显示,与治疗组比较,对照组胞浆电子密度降低,内质网扩大,部分线粒体嵴断裂,核周间隙增高,核浆比例增大均更加明显。结论:丹参酮抑制白细胞表面黏附分子CD 11a、CD 18、LFA 1的表达,阻断白细胞与血管内皮细胞黏附,在脑梗死治疗中具有保护神经细胞的作用。     

高压氧对一氧化碳中毒大鼠血小板CD61及多形核白细胞黏附分子CD11b/CD18表达的影响

背景：一氧化碳中毒后的脑损伤与白细胞在微血管上的黏附性及其与黏附分子发生的生化反应直接相关.目的：观察一氧化碳中毒后,高压氧治疗对大鼠外周血血小板CD61及多形核白细胞黏附分子CD11b/CD18表达的影响.设计：观察对比实验.单位：首都医科大学附属北京朝阳医院实验室.材料：实验于2002-01/03在首都医科大学附属北京朝阳医院实验室完成.选择健康成年Wistar大鼠128只,雌雄不拘.用抽签法随机分为4组,正常对照组8只,一氧化碳中毒组、高压对照组及高压氧治疗组各40只.其中后3组又分别分为一氧化碳中毒后、高气压处理后及高压氧处理后第1天（当日立即）,第5,10,15,20天5个时相组,每组8只.方法：将一氧化碳中毒组、高压对照组和高压氧治疗组大鼠分别暴露于体积分数为2.995&;#215;10-3一氧化碳下60 min,高压对照组给予0.2 MPa高压空气处理,高压氧治疗组给予给予0.2 MPa高压氧治疗1 h,1次/d.血标本采集分别在一氧化碳中毒后第1,5,10,15,20天早晨进行.麻醉大鼠后用心内注射的方式采血.应用流式细胞仪测定一氧化碳中毒大鼠在不同时间段外周血血小板CD61及多形核白细胞黏附分子CD11b/CD18的表达.CD61及CD11b/CD18表达均以平均荧光强度为单位定量测定.主要观察指标：①各组大鼠外周血血小板CD61相对表达量（荧光指数）的变化.②各组大鼠外周血多形核白细胞黏附分子CD11b/CD18相对表达量（荧光指数）的变化.结果：128只大鼠全部进入结果分析,无脱失.①各组大鼠外周血血小板CD61相对表达量（荧光指数）的变化：一氧化碳中毒组大鼠在一氧化碳中毒后第1,5,10天外周血血小板CD61相对表达量明显高于对照组（t=2.625～4.428,P＜0.05～0.01）;高气压组大鼠在高气压治疗后第1,5,10天的血小板CD61相对表达量显著高于对照组（t=2.586～2.704,P＜0.05）;高压氧组大鼠仅在高压氧处理后第1天血小板CD61的相对表达量高于对照组（t=2.947,P＜0.05）.②各组大鼠外周血多形核白细胞黏附分子CD11b/CD18相对表达量（荧光指数）的变化：一氧化碳中毒组大鼠外周血CD11b/CD18相对表达量在一氧化碳中毒后第1,5,10,15和20天均显著高于对照组（t=2.665～4.452,P＜0.05～0.01）.高气压组大鼠在高气压治疗后第1,5,10和15天的外周血CD11b/CD18相对表达量均显著高于对照组（t=3.124～4.627,P＜0.05～0.01）.高压氧组大鼠在高压氧处理后第1,5,10天的外周血CD11b/CD18相对表达量均显著高于对照组（t=3.549～4.223,P＜0.01）.结论：一氧化碳中毒后大鼠外周血血小板CD61及多形核白细胞黏附分子CD11b/CD18的表达增高并持续一段时间,高压氧能有效下凋血小板及细胞黏附分子的水平,可以进一步解释一氧化碳中毒后高压氧治疗的脑保护作用.     

高压氧对一氧化碳中毒大鼠血小板CD61及多形核白细胞黏附分子 CD11b/CD18表达的影响

背景一氧化碳中毒后的脑损伤与白细胞在微血管上的黏附性及其与黏附分子发生的生化反应直接相关.目的观察一氧化碳中毒后,高压氧治疗对大鼠外周血血小板CD61及多形核白细胞黏附分子CD11b/CD18表达的影响.设计观察对比实验.单位首都医科大学附属北京朝阳医院实验室.材料实验于2002-01/03在首都医科大学附属北京朝阳医院实验室完成.选择健康成年Wistar大鼠128只,雌雄不拘.用抽签法随机分为4组,正常对照组8只,一氧化碳中毒组、高压对照组及高压氧治疗组各40只.其中后3组又分别分为一氧化碳中毒后、高气压处理后及高压氧处理后第1天(当日立即),第5,10,15,20天5个时相组,每组8只.方法将一氧化碳中毒组、高压对照组和高压氧治疗组大鼠分别暴露于体积分数为2.995×10-3一氧化碳下60 min,高压对照组给予0.2 MPa高压空气处理,高压氧治疗组给予给予0.2 MPa高压氧治疗1 h,1次/d.血标本采集分别在一氧化碳中毒后第1,5,10,15,20天早晨进行.麻醉大鼠后用心内注射的方式采血.应用流式细胞仪测定一氧化碳中毒大鼠在不同时间段外周血血小板CD61及多形核白细胞黏附分子CD11b/CD18的表达.CD61及CD11b/CD18表达均以平均荧光强度为单位定量测定.主要观察指标①各组大鼠外周血血小板CD61相对表达量(荧光指数)的变化.②各组大鼠外周血多形核白细胞黏附分子CD11b/CD18相对表达量(荧光指数)的变化.结果128只大鼠全部进入结果分析,无脱失.①各组大鼠外周血血小板CD61相对表达量(荧光指数)的变化一氧化碳中毒组大鼠在一氧化碳中毒后第1,5,10天外周血血小板CD61相对表达量明显高于对照组(t=2.625～4.428,P＜0.05～0.01);高气压组大鼠在高气压治疗后第1,5,10天的血小板CD61相对表达量显著高于对照组(t=2.586～2.704,P＜0.05);高压氧组大鼠仅在高压氧处理后第1天血小板CD61的相对表达量高于对照组(t=2.947,P＜0.05).②各组大鼠外周血多形核白细胞黏附分子CD11b/CD18相对表达量(荧光指数)的变化一氧化碳中毒组大鼠外周血CD11b/CD18相对表达量在一氧化碳中毒后第1,5,10,15和20天均显著高于对照组(t=2.665～4.452,P＜0.05～0.01).高气压组大鼠在高气压治疗后第1,5,10和15天的外周血CD11b/CD18相对表达量均显著高于对照组(t=3.124～4.627,P＜0.05～0.01).高压氧组大鼠在高压氧处理后第1,5,10天的外周血CD11b/CD18相对表达量均显著高于对照组(t=3.549～4.223,P＜0.01).结论一氧化碳中毒后大鼠外周血血小板CD61及多形核白细胞黏附分子CD11b/CD18的表达增高并持续一段时间,高压氧能有效下凋血小板及细胞黏附分子的水平,可以进一步解释一氧化碳中毒后高压氧治疗的脑保护作用.     

电针刺内关穴对体外循环大鼠心肌的保护作用

目的研究电针刺内关穴对大鼠体外循环（CPB）后白细胞黏附分子的调节和对心肌细胞凋亡的作用，从而探讨电针刺对体外循环后心肌保护作用的机制。方法30只大鼠随机分为3组，对照组、体外循环组（CPB组）和针刺内关组（EA组）。体外循环组采用MackensenGB的方法建立大鼠的体外循环模型；电针刺组采用电针刺双侧内关穴并维持到术后1h。术中采血血气分析，流式细胞仪全血法测定白细胞表面CDllb表达，术后取心肌PT—PCR测定Bcl-2和BaxmRNA表达，Western印迹分析Bcl-2和Bax蛋白含量，并采用TUNEL法观察细胞凋亡。结果大鼠体外循环停循环后的不同时点白细胞（PMN）表面的黏附分子CD11b表达均明显升高，EA组PMN表面的黏附分子CD11b的表达明显下降。CPB后大鼠心肌细胞Bcl-2和BaxmRNA表达明显增强，EA组凋亡相关基因BaxmRNA表达明显降低，Bcl-2mRNA表达明显增加。CPB组心肌组织Bcl-2和Bax蛋白含量显著增高，EA组Bax蛋白表达明显降低，Bcl-2蛋白表达明显增加。CPB组心肌缺血再灌注损伤后心肌细胞凋亡数明显增加，EA组心肌凋亡细胞数与心肌缺血组相比明显减轻。结论电针内关穴可通过抑制凋亡，减轻体外循环下心肌组织的病理损伤，抑制炎症细胞的黏附，从而产生心肌保护作用。     

益气复脉粉针对内毒素诱导大鼠肠系膜微循环障碍的作用研究

目的探讨静脉给予益气复脉粉针对内毒素血症大鼠肠系膜微循环障碍的改善作用。方法将30只Wistar大鼠随机分为对照组、模型组、治疗组,每组10只。静脉注入脂多糖（LPS）10mg&#183;kg-1&#183;h-1复制内毒素血症微循环障碍模型,20min后治疗组连续静脉注射益气复脉粉针（80mg&#183;kg-1&#183;h-1）,对照组和模型组给予等量生理盐水。每20min动态观察大鼠肠系膜细静脉壁黏附白细胞数、细静脉壁过氧化物以及白蛋白渗出的变化,直至100min结束观察。检测肠系膜间质内肥大细胞脱颗粒率,用流式细胞仪测定外周血粒细胞黏附分子CD11b和CD18的表达,用免疫组化法检测肺组织细胞间黏附分子-1（ICAM-1）及核转录因子-KB（NF—kB）p65的表达。结果20min起模型组大鼠肠系膜细静脉壁黏附白细胞数、管壁过氧化物依存的二氢罗达明（DHR）荧光强度和白蛋白渗出均明显增加（均P〈0．05）;100min后肠系膜间质内肥大细胞脱颗粒率亦显著增加,外周血粒细胞黏附分子CD11b和CD18的表达明显增加,肺组织ICAM-1、NF—kBp65积分吸光度（A）值明显升高（均P〈0．05）。与模型组相比,治疗组40min后细静脉壁黏附自细胞数明显减少,细静脉壁过氧化物依存的DHR荧光强度增加明显受抑制,白蛋白渗出明显减少（均P〈0．05）;100min后肠系膜间质内肥大细胞脱颗粒率明显减少,外周血粒细胞黏附分子CD11b和CD18表达明显下降,肺组织ICAM-1、NF—kBp65积分A值明显降低（均P〈0．05）。结论益气复脉粉针对LPS诱导的肠系膜微循环障碍有改善作用,机制可能与其能解离白细胞与血管内皮黏附的作用有关,而该作用又可能与减少粒细胞黏附分子CD11b和CD18、血管内皮ICAM-1及NF—kBp65表达有关。     

Transient adhesion of neutrophils to endothelium

Fluorescently labeled polymorphonuclear leukocytes (PMN) were used to measure adhesion to human umbilical vein endothelial cells (EC) cultured in vitro. Stimulation of PMN with phorbol dibutyrate (PDB), TNF, or C5a caused an increase in adhesion followed by a return to prestimulation levels of adhesion of longer times of incubation. Maximal adhesion of PMN to EC occurred rapidly in response to C5a (5 min) and more slowly with TNF or PDB (15 min). PMN stimulated to adhere with C5a detached from EC by 15 min. PMN from CD11/CD18-deficient patients and PMN incubated with anti-CD18 mAbs failed to bind to EC despite maximal stimulation. Anti-CD11a/CD18 and anti-CD11b/CD18 each partially inhibited adhesion, and a combination of these two reagents completely blocked adhesion. The adhesion we measured was therefore completely dependent on CD11/CD18, and CD11a/CD18 and CD11b/CD18 each contributed to adhesion. Stimuli that enhanced adhesion of PMN to EC also enhanced expression of CD11b/CD18 on the cell surface, but the time course of expression correlated poorly with changes in adhesivity. To determine if changes in the expression of CD11b/CD18 are necessary for the changes in adhesivity, we used enucleate cytoplasts that did not increase expression of CD11b/CD18. Cytoplasts showed a normal rise and fall in adhesivity in response to PDB. We conclude that the transient adhesion of stimulated PMN to naive EC is regulated by changes in the nature of existing CD11/CD18 molecules on the PMN surface. Changes in expression of CD11b/CD18 may contribute to enhancement of adhesivity, but a definite role for this phenomenon has yet to be established.     

丹参注射液对急性胰腺炎大鼠肠道黏膜血流和细菌移位影响的实验研究

目的:观察丹参对急性胰腺炎(AP)大鼠肠道黏膜血流和肠道细菌移位的影响.方法:采用随机对照研究方法.向胰管内逆行加压注射牛磺胆酸钠制备AP模型;治疗药物用丹参注射液;分别观察正常组、假手术组、AP组及丹参治疗组大鼠肠道黏膜血流和肠道细菌移位率.结果:丹参治疗组和AP组肠道黏膜血流较正常组和假手术组均有不同程度降低;丹参治疗组大鼠肠道黏膜血流较AP组显著改善(P均<0.05).丹参治疗组和AP组肠道细菌移位率较正常组和假手术组均显著增加,而丹参治疗组肠道细菌移位率较AP组显著下降(P均<0.05).丹参治疗组死亡率较AP组显著降低(P<0.05).结论:丹参可显著改善AP大鼠肠道黏膜血流,降低肠道细菌移位率和死亡率.     

急性出血坏死性胰腺炎时细胞粘附分子表达对中性粒细胞在肺脏聚集的影响

目的：探讨急性出血坏死性胰腺炎（ＡＨＮＰ）时中性粒细胞（ＰＭＮ）聚集于肺脏的机制。方法：利用ＡＨＮＰ并发急性肺损伤（ＡＬＩ）大鼠模型,采用免疫组化技术等方法,动态观察ＡＨＮＰ后大鼠肺脏实质细胞间粘附分子１（ＩＣＡＭ１）、ＰＭＮ表面巨噬细胞分化抗原１（ＣＤ１１ｂ／ＣＤ１８）的表达改变和ＰＭＮ肺脏聚集的变化。结果：ＡＨＮＰ后,肺脏ＩＣＡＭ１表达逐渐增加,与ＰＭＮ肺脏聚集程度呈显著正相关,而ＰＭＮ表面ＣＤ１１ｂ／ＣＤ１８在ＡＨＮＰ后１小时即迅速表达至高峰,并持续２４小时保持此高表达状态。结论：ＡＨＮＰ后,ＰＭＮ在肺脏的大量聚集是建立在ＰＭＮ表面ＣＤ１１ｂ／ＣＤ１８与肺实质细胞ＩＣＡＭ１高表达的基础之上,而ＩＣＡＭ１为这一粘附过程中的可变因素,是影响ＰＭＮ粘附并聚集于肺脏的主要因素     

Dopamine attenuates the chemoattractant effect of interleukin-8: a novel role in the systemic inflammatory response syndrome

Activated neutrophil (PMN) adherence to vascular endothelium comprises a key step for both transendothelial migration and initiation of potentially deleterious release of PMN products. The biogenic amine, dopamine (DA), has been used for several decades in patients to maintain hemodynamic stability. The effect of dopamine on PMN transendothelial migration and adhesion receptor expression and on the endothelial molecules, E-selectin and ICAM-1, was evaluated. PMN were isolated from healthy controls, stimulated with lipopolysaccharide (LPS), and tumor necrosis factor-alpha (TNF-alpha) and treated with dopamine. CD 11b and CD 18 PMN adhesion receptor expression were assessed flow cytometrically. In a separate experiment, the chemoattractant peptide, IL-8, was placed in the lower chamber of transwells, and PMN migration was assessed. Human umbilical vein endothelial cells (HUVEC) were stimulated with LPS/TNF-alpha and incubated with dopamine. ICAM-1 and E-selectin endothelial molecule expression were assessed flow cytometrically. There was a significant increase in transendothelial migration in stimulated PMN compared with normal PMN (40 vs. 14%, P < 0.001). In addition, PMN CD11b/CD18 was significantly upregulated in stimulated PMN compared with normal PMN (252.4/352.4 vs. 76.7/139.4, P < 0.001) as were endothelial E-selectin/ICAM-1 expression compared with normal EC (8.1/9 vs. 3.9/3.8, P < 0.05). After treatment with dopamine, PMN transmigration was significantly decreased compared with stimulated PMN (8% vs. 40%, P < 0.001). Furthermore, dopamine also attenuated PMN CD11b/CD18 and the endothelial molecules E-selectin and ICAM-1 compared with stimulated PMN/EC that were not treated dopamine (174/240 vs. 252/352, P < 0.05 and 4/4.4 vs. 8.1/9, P < 0.05. respectively). The chemoattractant effect of IL-8 was also attenuated. These results identify for the first time that dopamine attenuates the initial interaction between PMN and the endothelium, and consequently, modulates PMN exudation. Thus, biogenic amines, including dopamine, may function as anti-inflammatory cytokines.     

Neutrophil-activating protein 1/interleukin 8 stimulates the binding activity of the leukocyte adhesion receptor CD11b/CD18 on human neutrophils

The cytokine NAP-1/IL-8 is produced by a variety of different cells in response to inflammatory stimuli and elicits several biological responses from PMN. Experiments presented here demonstrate that PMN exposed to NAP-1/IL-8 expressed increased amounts of CD11b/CD18, as well as CD11c/CD18 and CR1, on their cell surface, while expression of Fc gamma RIII and HLA-A,B,C remained essentially unchanged. Increased CD11b/CD18 and CD11c/CD18 appears to correspond with the release of specific granules by NAP-1/IL-8. NAP-1/IL-8 was also a potent stimulator of several of the binding activities of CD11b/CD18. Ligation of EC3bi by CD11b/CD18 was rapidly enhanced by NAP-1/IL-8, but phagocytosis of the ligated particles was not induced by the agonist. In addition, enhanced binding of EC3bi was observed in the absence of an increase in receptor expression as shown with PMN cytoplasts. NAP-1/IL-8 promoted additional adhesive interactions between CD11b/CD18 and the biosynthetic precursor of LPS, lipid IVa, fibrinogen, and endothelial cells, suggesting that NAP-1/IL-8 may promote leukocyte adhesion in vivo that could lead to recruitment of PMN to sites of tissue inflammation.     

复方丹参注射液治疗急性汞中毒的实验研究

目的：探讨复方丹参注射液对急性汞中毒的治疗作用。方法：采用皮下注射１０ｇ／Ｌ氯化高汞（１．７ｍｌ／ｋｇ）引起家兔急性汞中毒的动物模型（汞中毒组），测定血浆及组织匀浆中丙二醛（ＭＤＡ）含量及肺组织中卵磷脂（ＰＣ）和总磷脂（ＴＰＬ）含量，同时检测血尿素氮（ＢＵＮ）浓度及尿常规；并与中毒后复方丹参注射液组（治疗组）和生理盐水对照组比较。结果：汞中毒后２４小时血浆和组织中ＭＤＡ含量均明显增加（Ｐ＜０．０５或Ｐ＜０．０１）；血ＢＵＮ浓度升高，与汞中毒前及对照组比较均有显著性差异（Ｐ均＜０．０１）；尿蛋白及尿镜检均为（＋＋＋＋）；肺组织ＰＣ及ＴＰＬ含量与对照组比较均明显减少（Ｐ均＜０．０１）。注射氯化高汞后给予复方丹参注射液可减少ＬＰＯ生成，降低ＢＵＮ水平，逆转尿的改变，且能防止肺表面活性物质（ＰＳ）减少。结论：急性汞中毒后不仅损害肾脏，而且累及肺脏，其ＰＳ减少可能与ＭＤＡ增加有关；复方丹参注射液能抑制这一过程，进而减轻汞的致毒效力     

Leukocyte adhesion-deficient neutrophils fail to amplify phagocytic function in response to stimulation. Evidence for CD11b/CD18-dependent and -independent mechanisms of phagocytosis.

Stimulation of PMN with inflammatory mediators markedly augments Fc and CR1 receptor-mediated ingestion. However, CD11/CD18-deficient PMN from three patients with complete leukocyte adhesion deficiency (LAD) failed to recruit phagocytic function in response to phorbol esters, cytokine, or Arg-Gly-Asp-containing ligand stimulation. Because stimulated ingestion is protein kinase C (PKC)-dependent, our data indicate that LAD PMN exhibit only PKC-independent phagocytosis. The defect in PKC-dependent ingestion is specific for CD11b/CD18 and not secondary to the chronic or recurrent infections which occur in this disease. The LAD phenotype for phagocytic function can be reproduced in normal PMN by the anti-CD11b MAbs OKM1 and OKM10. In contrast, MAb Mo1 (anti-CD11b) and MAb IB4 (anti-CD18) inhibit both CD11b/CD18-dependent and -independent mechanisms of ingestion by normal PMN. Their ability to inhibit CD11b/CD18-independent ingestion may be mediated by cAMP, as shown by experiments with a protein kinase A inhibitor HA1004 and by direct measurement of cAMP levels in immune complex- and FMLP-stimulated PMN. These data indicate that CD11b/CD18-independent and -dependent mechanisms of phagocytosis exist and that some effects of anti-CD11b/CD18 MAbs may be mediated by alterations in cAMP levels.     

CD18-independent neutrophil and mononuclear leukocyte emigration into the peritoneum of rabbits.

The CD18 mAb 60.3 and the CD49d mAb HP1/2 were given at the time of intraperitoneal instillation of either protease peptone or live Escherichia coli bacteria and at 12 h. Leukocyte emigration was evaluated at 4 and 24 h. PMN emigration 4 h after protease peptone instillation and injection of both mAbs was 10% of that in saline treatment. It was 15% of that in saline treatment after mAb 60.3 alone and unchanged by mAb HP1/2. At 24 h PMN emigration in response to protease peptone was not prevented by either CD18 or CD49d mAbs, however, when given together emigration was 10% of saline-treated animals. Mononuclear cell emigration to protease peptone was enhanced at 4 h by both CD18 and CD49d mAbs. The CD18 mAb did not augment mononuclear emigration in response to live bacteria. At 24 h, neither the CD18 nor the CD49d mAb alone blocked emigration of mononuclear cells, but the combination of the two did. These studies demonstrate that: (a) early (4 h) PMN emigration is CD11/CD18 dependent; (b) late (24 h) PMN emigration is CD11/CD18 independent; and (c) mononuclear cells utilize the integrins CD18 and CD49d.     

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.