阿托伐他汀对高脂血症患者白细胞补体调节蛋白表达的影响

目的观察阿托伐他汀对高脂血症患者白细胞补体调节蛋白表达的影响。方法高脂血症患者25例采用阿托伐他汀治疗8~12w,应用流式细胞仪测定治疗前后外周血白细胞补体调节蛋白CD55、CD59的表达。结果高脂血症患者CD55阳性淋巴细胞平均荧光强度低于对照组〔(2.03±0.30)vs(2.27±0.42),P<0.05〕,白细胞CD59表达水平与对照组无显著差异;治疗8~12 w,CD59阳性淋巴细胞、单核细胞、粒细胞平均荧光强度均显著升高〔(4.34±1.14)vs(3.69±0.74),(4.51±1.33)vs(3.89±0.88),(5.65±1.68)vs(4.65±0.98);P<0.01,P<0.05,P<0.01〕,治疗前后白细胞CD55表达水平无明显变化。结论高脂血症患者淋巴细胞CD55表达水平较正常人降低,CD59与正常人无明显差别,阿托伐他汀治疗可上调CD59表达,但对CD55表达无明显影响。     

阿托伐他汀对高脂血症患者补体调节蛋白CD35的影响

目的探讨他汀类调脂药物对高脂血症患者外周血白细胞补体调节蛋白CD35表达的影响及在动脉粥样硬化疾病中的作用。方法选高脂血症患者23例,年龄、性别、体重指数匹配的正常人20例作为对照,用流式细胞术测定外周血白细胞CD35的表达。高脂血症患者使用阿托伐他汀治疗,观察治疗8周后CD35的变化。结果高脂血症患者CD35阳性白细胞、百分率较正常对照组升高(18.40%比12.90%,P<0.05);阿托伐他汀治疗后,CD35阳性白细胞、淋巴细胞、单核细胞、粒细胞平均荧光强度与治疗前比较明显升高(2.02比1.47,3.16比1.60,2.03比1.44,2.05比1.46,P均<0.05),与正常对照组比较亦升高(2.02比1.47,3.16比1.67,2.03比1.52,2.05比1.48,P均<0.05);CD35阳性、淋巴细胞百分率治疗后较治疗前及正常对照组比较均升高(4.93%比3.95%,4.93%比3.35,%,P均<0.05)。结论阿托伐他汀治疗可增加高脂血症患者外周血白细胞补体调节蛋白CD35的表达,提示上调补体调节蛋白的表达可能是他汀类药物延缓动脉粥样硬化进展新的作用机制。     

高脂血症患者血清补体C3、C4、备解素和白细胞补体调节蛋白CD35、CD55、CD59的表达

目的:探讨高脂血症患者血清补体和外周血白细胞补体调节蛋白的表达及其在动脉粥样硬化中的意义。方法:选高脂血症患者46例(高脂血症组),年龄、性别、体重指数匹配的正常人20例作为正常对照组,用免疫散射比浊法测血清补体C3、C4、备解素(Pf);用流式细胞术测定外周血中性粒细胞、淋巴细胞和单核细胞CD35、CD55、CD59的表达,观察上述指标在高脂血症组中的变化,分析影响因素。结果:高脂血症组血清C3、C4、Pf水平较正常对照组明显升高(P<0.01);补体C3、C4水平与血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)明显正相关(P<0.01),Pf与TC、LDLC正相关(P<0.01)。CD35阳性淋巴细胞、单核细胞、粒细胞百分率较正常对照组升高(P<0.05),CD35阳性淋巴细胞、粒细胞百分率与TG呈正相关(P<0.05～0.01);CD55阳性淋巴细胞平均荧光强度较正常对照组下降(P<0.05);CD59阳性淋巴细胞、单核细胞百分率较正常对照组下降(P<0.05)。结论:高脂血症患者血清补体C3、C4、Pf升高,白细胞补体调节蛋白表达改变,补体及补体调节蛋白的改变与血脂水平相关,表明脂代谢紊乱可影响补体及补体调节蛋白的表达,提示补体及补体调节蛋白可能参与动脉粥样硬化的病理生理过程。     

老年高脂血症患者补体调节蛋白CD55、CD59与踝臂指数的关系研究

目的探讨老年高脂血症患者补体调节蛋白CD55、CD59与踝臂指数(ABI)的关系。方法选择老年高脂血症患者243例,正常对照者60例,测定补体调节蛋白CD55、CD59的表达及ABI,分析其关系。结果与正常对照组比较,高脂血症组补体调节蛋白CD55阳性淋巴细胞平均荧光强度及百分率明显降低(P<0.05);CD55阳性淋巴细胞平均荧光强度与腰臀比、腰围、体质量指数呈负相关(P<0.05);高脂血症组ABI较正常对照组明显降低(P<0.05);ABI与年龄、高敏C反应蛋白、总胆固醇、收缩压、体质量指数呈负相关(P<0.05),与CD55阳性淋巴细胞平均荧光强度呈正相关(P<0.05),与补体调节蛋白CD59不相关。结论老年高脂血症患者ABI减低,ABI减低与补体调节蛋白CD55表达降低相关,与补体调节蛋白CD59无关。     

高脂血症患者血清抵抗素水平及与补体调节蛋白CD55、CD59表达的关系

目的观察高脂血症患者血清抵抗素与补体调节蛋白的表达的关系。方法高脂血症患者50例,年龄、性别、体重与其匹配的健康对照21例,使用酶联免疫法测定空腹血清抵抗素浓度,使用流式细胞仪测定外周血白细胞CD55、CD59的表达。结果高脂血症患者空腹血清抵抗素浓度较正常对照增高（P〈0.05）,女性血清抵抗素浓度高于男性（P〈0.05）,抵抗素与血清总胆固醇明显正相关（r=0.297,P〈0.05）,与体重指数、腰臀比、血糖均无相关性,与补体调节蛋白CD55、CD59阳性细胞平均荧光强度及百分率亦无相关性。多元回归分析腰臀比是CD55阳性淋巴细胞平均荧光强度的独立预测因子,腰围是CD55阳性单核细胞百分率的独立预测因子。结论高脂血症患者空腹血清抵抗素浓度增高,有性别差异,且与血清总胆固醇明显正相关,提示抵抗素可能参与脂代谢紊乱。高脂血症者补体调节蛋白表达下调,且与腰臀比、腰围密切负相关,提示肥胖,特别是中心型肥胖可影响补体调节蛋白的表达。空腹血清抵抗素与补体调节蛋白CD55、CD59表达无相关性,是否有其他脂肪细胞因子参与影响补体调节蛋白的表达有待进一步研究。     

高脂血症患者补体调节蛋白CD55、CD59表达与脂肪细胞因子的关系研究

目的 探讨高脂血症患者补体调节蛋白CD55、CD59的表达与脂肪细胞因子瘦素、脂联素、抵抗素水平的变化及其关系.方法 高脂血症患者50例,年龄、性别、体重与其匹配的健康对照21例,用流式细胞术测定外周血白细胞CD55、CD59的表达,用酶联免疫法测定血浆瘦素、脂联素,血清抵抗素浓度,分析CD55、CD59和脂肪细胞因子在高脂血症中的变化及其关系.结果 高脂血症患者CD55阳性淋巴细胞平均荧光强度(MFI)较健康对照组下降(P＜0.05),瘦素较健康对照组升高(P ＜0.05),脂联素较健康对照组下降(P＜0.05);CD55阳性淋巴细胞MFI与腰围、腰臀比值呈负相关(均P＜0.05),与脂联素呈正相关(P＜0.05).结论 高脂血症患者补体调节蛋白CD55表达下调,可能与腹部脂肪分布、脂联素有关,脂联素可能影响补体调节蛋白CD55的表达.     

高脂血症患者瘦素与补体调节蛋白CD55、CD59的关系研究

目的观察高脂血症患者血浆瘦素水平和补体调节蛋白CD55、CD59表达的关系。方法选高脂血症患者58例,年龄、性别、体重相匹配正常人21名作为对照,用ELISA法测定血浆瘦素,用流式细胞术测定外周血白细胞补体调节蛋白CD55及CD59的表达,分析瘦素水平和补体调节蛋白表达之间的关系。结果与正常对照比较,高脂血症患者血浆瘦素较正常对照组明显升高(非正态分布,中位数为8357 ng/L比5348 ng/L,P=0.024);高脂血症患者淋巴细胞CD55平均荧光强度及百分率较正常对照组明显下调[(2.07±0.26)比(2.34±0.44),(35.72±13.53)%比(44.14±15.67)%,P=0.012,0.022];血浆瘦素与TC、LDL、TG、体重指数、腰围及臀围正相关(r=0.285-0.451,P=0.011-0.000),与补体调节蛋白CD55、CD59表达不相关(P>0.05)。结论高脂血症患者血浆瘦素浓度升高,白细胞补体调节蛋白CD55表达下调,但瘦素水平与补体调节蛋白表达水平之间无数量关系,因此,瘦素可能不直接影响补体调节蛋白表达。     

补体C3、C4、备解素及补体调节蛋白CD55、CD59与颈动脉内膜中层厚度的关系研究

目的:探讨补体及补体调节蛋白与颈动脉内膜中层厚度(IMT)的关系。方法:选高脂血症患者57例(高脂血症组),正常对照20人(正常对照组),测定补体C3、C4、备解素(Pf)水平、补体凋节蛋白CD55、CD59的表达及颈动脉IMT,分析其关系。结果:与正常对照组比较,高脂血症组补体C3、C4及备解素、颈动脉IMI、明显升高,补体调节蛋白CD55阳性淋巴细胞平均荧光强度减低;IMT与年龄、收缩压、腰臀比值、高敏C反应蛋白正相关,与补体调节蛋白CD55阳性淋巴细胞平均荧光强度负相关,与补体C3、C4、备解素及补体调节蛋白CD59不相关。结论:颈动脉IMT增厚与补体调节蛋白CD55表达降低相关,而与补体C3、C4、备解素、补体调节蛋白CD59无直接关系。     

高脂血症中脂联素水平与CD55、CD59表达的关系研究

动脉粥样硬化是一种慢性炎性病变，补体在其发生、发展中起重要作用。补体调节蛋白抑制补体活化过程，在一定程度上可防止组织损伤，但补体调节蛋白表达的影响因素目前还不清楚。本研究通过观察高脂血症患者补体调节蛋白CD55 CD59的表达和脂联素的关系，探讨补体调节蛋白表达的调节机制。     

阿托伐他汀对高胆固醇饮食兔动脉粥样硬化病变的影响及其机制

目的探讨阿托伐他汀对兔早期动脉粥样硬化病变的影响及其机制。方法利用高胆固醇饮食建立动脉粥样硬化兔模型后,随机给予阿托伐他汀每天1.5 mg/kg或淀粉,2周后测定主动脉的内膜、中膜厚度和内膜中膜厚度比。采用原位杂交法检测动脉壁单核细胞趋化蛋白1 mRNA的表达情况。采用酶联免疫吸附法检测血浆中白细胞介素6的水平。结果血浆白细胞介素6水平与血浆低密度脂蛋白胆固醇水平呈显著正相关(r=0.852,P<0.01)。与淀粉组比较,阿托伐他汀组外周血白细胞介素6水平显著降低55%,动脉粥样硬化面积明显减少(52.5%±4.2%比81.9%±2.8%,P<0.01),内膜厚度显著降低(24.18±10.21μm比77.51±22.47μm,P<0.01),内膜单核细胞趋化蛋白1阳性细胞数显著减少(29±5个/HP比49±17个/HP,P<0.01)。动脉内膜厚度与其单核细胞趋化蛋白1阳性细胞数显著相关(r=0.831,P<0.01)。结论高胆固醇血症可诱发炎症反应,阿托伐他汀具有抗动脉粥样硬化效应,该效应不仅与降低血浆胆固醇水平相关,而且与其降低血浆白细胞介素6水平、减少动脉壁单核细胞趋化蛋白1表达密切相关。     

Increased expression of activation markers on monocytes and neutrophils in type 2 diabetes

BACKGROUND: Activation of leukocytes is obligatory for adherence to the endothelium and atherogenesis. Since leukocyte activation by triglycerides (TG) and glucose has been described in vitro, we hypothesised higher leukocyte activation in patients with type 2 diabetes. METHODS: Using flow cytometry, we studied the expression of the leukocyte activation markers CD11A, CD11B, CD62L and CD66B in 15 patients with type 2 diabetes without clinical evidence of atherosclerosis (55+/-7 years) and in 15 healthy controls (53+/-2 years). All patients were on oral antidiabetic treatment (glyHb 6.3+/-0.9%) and not taking statins or anti-inflammatory drugs. RESULTS: In comparison with controls, the patients had a higher waist circumference (1.08+/-0.09 vs 0.94+/-0.11 m, p<0.005) and higher fasting glucose (8.4+/-2.3 vs 5.3+/-0.7 mM, p<0.005), whereas fasting plasma lipids were not statistically different. The leukocyte count was higher in the patients (6.55+/-1.55 vs 5.07+/-1.10 x 10(9) cells/l, p<0.005) due to higher neutrophils and lymphocytes (+34% and +24%, p<0.05 for each). CD11B on monocytes and CD11B and CD66B on neutrophils were higher in the patients (+30%, +52% and +43%, P<0.05 for each). Fasting glucose, waist circumference, body mass index and systolic blood pressure were positively associated with the leukocyte and neutrophil count. The expressions of CD11B and CD66B on monocytes and neutrophils were strongly positively interrelated, but unrelated to TG and glucose. CONCLUSION: In patients with type 2 diabetes, the expression of activation markers on monocytes and neutrophils is enhanced and not correlated to fasting glucose or TG. These results suggest a proinflammatory situation in type 2 diabetes and most likely represent increased adhesive capacity of neutrophils and monocytes to the endothelium.     

Expression of CD55 and CD59 on peripheral blood cells in patients with lymphoproliferative disease of granular lymphocytes

Lymphoproliferative disease of granular lymphocytes (LDGL) is a disorder characterized by the clonal expansion of granular lymphocytes. It has recently been shown that the clonal expansion of granular lymphocytes occurs in patients with paroxysmal nocturnal hemoglobinuria (PNH) in a subclinical fashion. To test the possibility that LDGL patients share a PNH phenotype, we obtained peripheral blood cells from 20 patients with LDGL and examined the expression of the glycosylphosphatidyl inositol (GPI)-anchored proteins, CD55 and CD59. Compared with normal controls, however, a defective expression of CD55/59 was not observed on either granulocytes or erythrocytes from LDGL patients. An unexpected finding was the significantly lower CD55/59 expression on granular lymphocytes from patients with CD16(+)CD56(-) phenotype LDGL than from patients with CD16(+)CD56(+) phenotype LDGL, or natural killer (NK) and NK/T lymphocytes from healthy individuals. The positive correlation between the expression of CD56 and CD55/59 might have some relevance to the functional properties of the CD56(+) subset of large granular lymphocytes.     

Varying populations of CD59-negative,partly positive,and normally positive blood cells in different cell lineages in peripheral blood of paroxysmal nocturnal hemoglobinuria patients

CD59-antigen expression on the surface membranes of erythrocytes, granulocytes, monocytes, lymphocytes, and platelets was determined by flow cytometry in 34 healthy controls and 17 patients with paroxysmal nocturnal hemoglobinuria (PNH). In all PNH patients, CD59-negative erythrocytes accounted for > 10% of the total erythrocyte population. Two erythrocyte populations (CD59-negative and normally positlve or CD59-negative and partly positive), three populations (CD59-negative, partly positive, and normally positive), and one population (CD59-negative) were demonstrated in ten, six, and one patients, respectively. However, CD59-negative granulocytes did not account for > 10% of the total granulocytes in two patients, and one of them had only a CD59 normally positive granulocyte population. A particular granulocyte population extended over both CD59-negative and partly positive areas was shown in two patients. Two populations (CD59-negative and normally positive) and one population (CD59-negatlve) were demonstrated in monocytes and lymphocytes. CD59-negative lymphocytes accounted for >50% of the total lymphocytes in only two patients. Three patients had a CD59 normally positive lymphocyte population. Percentages of CD59-positive platelet population in normal controls were widely various. Therefore, it was usually difficult to discriminate between PNH-affected and normal platelets. Thus, the flow cytometric profiles of CD59-antigen expression varied not only between PNH patients but between cell lineages. The present results and our prior study indicate that CD59 flow cytometry using erythrocytes and granulocytes is most suitable for diagnosing PNH. © 1994 Wiley-Liss, Inc.     

The effect of low-dose atorvastatin on circulating monocyte chemoattractant protein-1 in patients with type 2 diabetes complicated by hyperlipidemia

The effect of low-dose atorvastatin on various biomarkers was investigated in patients with type 2 diabetes complicated by hyperlipidemia. At 0 and 12 weeks in both the atorvastatin group (10 mg/d; n=17) and the no-drug group (n=10), high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein (MCP)-1, plasminogen activator inhibitor (PAI)-1, and fibrinogen were measured. At baseline, the entire group of diabetic patients (n=27) had significantly higher values of hsCRP and fibrinogen compared with those in age-matched healthy subjects (n=29): 0.801 (0.306, 1.760) vs 0.282 (0.143, 0.6505) mg/L, P=.0042; 329.1+/-55.0 vs 212.4+/-35.9 mg/dL, P<.0001, respectively. High-sensitivity C-reactive protein decreased significantly with atorvastatin treatment, from 0.801 (0.243, 1.865) to 0.308 (0.200, 0.804) mg/L (P=.0191). Although MCP-1, PAI-1, and fibrinogen did not decrease in the atorvastatin patients overall, the decrease of MCP-1 was significant in women (n=10; from 241.9+/-45.8 to 215.4+/-49.5 pg/mL, P=.0332). No correlation was found between changes in the serum lipid concentrations and changes in hsCRP, MCP-1, PAI-1, or fibrinogen in either the atorvastatin or the no-drug group. In conclusion, low-dose atorvastatin (10 mg/d) significantly decreased hsCRP in patients overall, and MCP-1 was also decreased in women. These findings suggest the possibility that atorvastatin provides an anti-inflammatory effect even at a low dose.     

Expression of CD61 (beta3 integrin subunit) on canine cells

A monoclonal antibody (JM2E5) specific for the integrin beta3 chain, or CD61 or GPIIIa subunit, has been employed to determine the expression of the canine homologue CD41/CD61 or CD51/CD61 complex on different canine cells in peripheral blood lymphocytes, monocytes, granulocytes, platelets, erythrocytes, lymph-node cells, spleen cells and breast tumour cells). The canine homologue CD41/CD61 or CD51/61 was present on peripheral blood lymphocytes, monocytes, granulocytes, breast tumour cells and spleen cells as well as on platelets and it was absent from erythrocytes and lymph-node cells. An antigen with components of molecular masses of 25/100/120 kDa (under reducing conditions) was immunoprecipitated from canine peripheral lymphocytes and platelets, but not from granulocytes or monocytes. Expression on canine lymphocytes of the canine homologue of the human beta3 integrin chain was unexpected, based on the expression pattern of this molecule in human tissue.     

Expression of monocyte and lymphocyte adhesion molecules is increased in isolated coronary artery ectasia

BACKGROUND: Coronary artery ectasia is defined as localized or diffuse dilation of the coronary arteries exceeding the 1.5-fold of normal adjacent segment. Scarce data are available about the role of inflammation in coronary artery ectasia. In the present study, we aimed to evaluate the expression of CD11b and CD45 adhesion molecules in peripheral blood granulocytes, monocytes and lymphocytes from the patients with coronary artery ectasia as possible indicators of inflammation. METHOD: The study consisted of 14 patients who had angiographically normal coronary arteries with coronary artery ectasia and 13 age and sex-matched controls without coronary artery ectasia. Cell surface adhesion molecules were detected by direct immunofluorescence evaluated by flow cytometry using monoclonal antibodies tagged with fluorescent markers. Venous blood samples were taken after coronary angiography. RESULTS: Mean fluorescence intensity of CD45 (33.8+/-3.1 vs. 13.0+/-0.7, P<0.001) and CD11b (39.1+/-13.5 vs. 19.5+/-1.32, P<0.001) on the monocyte surface of patients with coronary artery ectasia were higher than those of controls. Similarly in patients with coronary artery ectasia, the expression of CD11b (7.5+/-0.61 vs. 5.6+/-0.2, P=0.009) and CD45 (47.5+/-3.6 vs. 36.2+/-2.5, P=0.02) on lymphocytes was also significantly higher than those of controls. CONCLUSION: Increased levels of cellular adhesion molecules in patients with coronary artery ectasia may be an indicator of endothelial activation and inflammation and are likely to be in the causal pathway leading to coronary artery ectasia.     

2型糖尿病患者补体调节蛋白CD55、CD59水平的变化及其意义

选2型糖尿病患者33例，24名健康自愿者作为对照，检测外周血白细胞CD55、CD59的表达．探讨其与糖尿病肾病的关系。2型糖尿病患者CD55、CD59表达下词，糖尿病病程、CD55阳性单核细胞平均荧光强度是尿白蛋白排泄率（UAER）的独立预测因素。补体调节蛋白表达减低可能与糖尿病肾病的发生有关。     

骨髓粒细胞与红细胞表面CD55 CD59缺失对血液疾病的诊断意义研究

目的探讨骨髓粒细胞、红细胞表面糖基化磷脂酰肌醇(GPI)锚定蛋白CD55、CD59缺失(CD55-、CD59-,也称PNH细胞)在血液系统疾病中的意义。方法采用流式细胞仪检测中山大学附属第一医院血液科2008年9月至2010年11月诊治的正常人、阵发性睡眠性血红蛋白尿、再生障碍性贫血(AA)、骨髓增生异常综合征(MDS)、急性髓细胞白血病(AML)、多发性骨髓瘤(MM)及营养不良性贫血患者外周血及骨髓中红细胞和粒细胞CD55、CD59缺失,并对结果进行分析。结果正常人骨髓粒细胞CD55-高于外周血(P<0.05);PNH患者骨髓红细胞CD55-、CD59-高于外周血(P<0.05);正常人、AA、MDS、AML、MM及营养不良性贫血各组间骨髓粒细胞CD55-表达无显著差异(P>0.05)。结论单一骨髓粒细胞CD55-表达升高特异性差。