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。     

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。     

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。     

阿托伐他汀对高脂血症患者补体调节蛋白CD55、CD59表达的影响

目的观察高脂血症患者补体调节蛋白CD55、CD59的表达及其与补体活化、脂代谢紊乱之间的关系,并探讨阿托伐他汀对其的影响。方法高脂血症患者67例,年龄、性别、体重与其匹配的健康对照24例,使用流式细胞仪测定外周血白细胞CD55、CD59的表达,分析CD55、CD59表达水平与血脂、补体活化指标、炎症因子及相关临床指标间的关系,对其中24例高脂血症患者使用阿托伐他汀治疗8~12周,观察治疗前后CD55、CD59表达的变化。结果高脂血症患者CD55阳性淋巴细胞、单核细胞平均荧光强度(MFI)低于健康对照组(2.07±0.28比2.29±0.44及3.45±1.02比4.33±2.32,P<0.01及P<0.05),CD55阳性淋巴细胞MFI与腰围、腰臀比值、高敏C反应蛋白、补体C5a呈负相关,与血脂不相关;补体C5a水平与CD55阳性淋巴细胞、单核细胞、粒细胞MFI负相关,与TG和舒张压正相关,与CD59表达指标不相关;阿托伐他汀治疗后CD59阳性淋巴细胞、单核细胞、粒细胞MFI增加(4.34±1.16比3.69±0.76,4.52±1.36比3.91±0.89,5.67±1.72比4.56±1.03,P<0.05,P<0.05及P<0.01),与血脂变化不相关。结论高脂血症患者补体调节蛋白CD55表达下调,可能与肥胖、腹型脂肪分布、炎症状态有关,不受血脂的直接影响;CD55表达水平与补体活化有关;阿托伐他汀干预可使CD59表达上调,与调脂作用无关。     

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。     

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。     

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。     

高脂血症患者瘦素与补体C3、C4及备解素关系的研究

目的观察高脂血症患者瘦素、补体C3、C4及备解素(Pf)表达水平变化以及它们之间的关系。方法选取高脂血症患者31例,年龄、性别、体重相匹配正常人18例作为对照,用酶联免疫夹心法(ELISA法)测定血浆瘦素,用免疫散射比浊法检测血清补体C3、C4及Pf,分析瘦素与补体C3、C4及Pf表达水平之间的关系。结果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8849.50pg/mlvs5909.25pg/ml,P=0.039);高脂血症患者血清补体C3、C4及Pf较正常对照组明显升高(1.63±0.39)g/Lvs(1.31±0.29)g/L,(0.42±0.14)g/Lvs(0.33±0.10)g/L,(0.45±0.09)g/Lvs(0.39±0.06)g/L,P=0.004,0.014,0.017;血浆瘦素与补体C3(r=0.420,P=0.003)及Pf(r=0.435,P=0.002)呈正相关,与补体C4的表达不相关(P>0.05)。结论瘦素可能影响补体的表达和激活。     

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.     

老年高脂血症患者补体C3、C4、备解素与踝臂指数的关系

目的 探讨老年高脂血症患者补体与踝臂指数(ABI)的关系.方法 选老年高脂血症患者257例,正常对照组60例,测定补体C3、C4、备解素(Pf)水平及ABI,分析其关系.结果 与对照组比较,高脂血症组C3 、C4 、Pf明显升高[(1.46 ±0.40)g/L vs (1.21 ±0.26) g/L,(0.37±0.14) g/L vs (0.29 ±0.09)g/L,(0.39±0.11)g/L vs (0.35±0.06)g/L,P=0.000,0.000,0.007];ABI降低[(1.12±0.15) vs(1.21±0.11),P=0.037],ABI与年龄(r=-0.243,P ＜0.05)、hsCRP(r=-0.330,P＜0.01)、性别(r=-0.284,P＜0.05)、TC(r=-0.276,P＜0.01)、收缩压(r=-0.228,P＜0.05)负相关,ABI与BMI正相关(r=0.257,P＜0.05),ABI与血清补体C3、C4、Pf不相关.结论 老年高脂血症患者ABI减低,ABI减低与补体C3、C4、Pf无直接关系.     

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。     

Complement activation in sickle cell disease: Dependence on cell density,hemolysis and modulation by hydroxyurea therapy

The complement system is an innate immune defense cascade that can cause tissue damage when inappropriately activated. Evidence for complement over activation has been reported in small cohorts of patients with sickle cell disease (SCD). However, the mechanism governing complement activation in SCD has not been elucidated. Here, we observe that the plasma concentration of sC5b-9, a reliable marker for terminal complement activation, is increased at steady state in 61% of untreated SCD patients. We show that greater complement activation in vitro is promoted by SCD erythrocytes compared to normal ones, although no significant differences were observed in the regulatory proteins CD35, CD55, and CD59 in whole blood. Complement activation is positively correlated with the percentage of dense sickle cells (DRBCs). The expression levels of CD35, CD55, and CD59 are reduced in DRBCs, suggesting inefficient regulation when cell density increases. Moreover, the surface expression of the complement regulator CD46 on granulocytes was inversely correlated with the plasma sC5b-9. We also show increased complement deposition in cultured human endothelial cells incubated with SCD serum, which is diminished by the addition of the heme scavenger hemopexin. Treatment of SCD patients with hydroxyurea produces substantial reductions in complement activation, measured by sC5b-9 concentration and upregulation of CD46, as well as decreased complement activation on RBCs in vitro. In conclusion, complement over activation is a common pathogenic event in SCD that is associated with formation of DRBCs and hemolysis. And, it affects red cells, leukocytes and endothelial cells. This complement over activation is partly alleviated by hydroxyurea therapy.     

X-Irradiation Does Not Affect the Levels of Complement Regulatory Proteins, CD35 (CR1), CD55 (DAF) and CD59 on Concentrated Red Cells

Human erythrocytes express complement (C) regulatory proteins, C3b/C4b receptor (CR1, CD35), decay-accelerating factor (DAF, CD55) and CD59, which protect cells from autologous C attack [ 1 ]. CR1 and DAF are C3-step regulators which destabilize the classical and alternative C3 convertases [ 1 ]. In addition, CR1 can bind C4b and C3b in the immune complexes to clear them from the circulation, namely immune adherence [ 2 ]. CD59 inhibits the formation of membrane attack complexes [ 1 ].     

A Flowcytometry Study of CD55 and CD59 Expression on Erythrocytes in Rheumatoid Arthritis Patients

Background: Inappropriate activation or blockage of the inhibition of complement system could cause tissue damages in autoimmune diseases particularly rheumatoid arthritis (RA). Defect in complement component regulation may cause damages to tissues, on the other hand, or the damaged tissue might affect the unnecessary activation of complement components.   Objective: To investigate the expression of CD55 and CD 59 complement regulatory proteins in RA patients. Subjects and Methods: Fifty proved rheumatoid arthritis patients participated in this study and their blood were collected for investigations. CD55 and CD59 molecules expression on the erythrocytes was assayed using primary monoclonal antibody and secondary FITC conjugated Ab, then the prepared samples were run with a FACSCalibur flowcytometer (Becton-Dickinson) and the obtained data was analyzed using a Cell Quest software package. To evaluate the complement function, CH50 was performed using patient sera. All experiments were done with a matched healthy volunteer group.   Results: The mean fluorescence intensity for CD55 was 27.6 ± 13.4 arbitrary unit for patients and 68.5 ± 10.5 for healthy group. CD59 mean fluorescence intensity was 314 ± 83 in patient group and 508 ± 56 in healthy volunteers. In addition, there was a significant difference between CH50 in patients (54.5 ± 15.5) and in healthy group (110 ± 20). A significant correlation between CD55 and CD59 expansion on the patient erythrocytes was found (P = 0.00, r = 0.576). No association was found between CD59, or CD55 with CH50 (P > 0.05).   Conclusion: The expression of CD55 and CD59 is down-regulated on erythrocytes of patients with RA. Change in expression of regulatory complement components in RA may be a useful key for the assessment of disease progression or in patients' follow-up.     

Expression of complement regulatory proteins CR1, DAF, MCP and CD59 in haematological malignancies

Host cells are protected from the lytic effect of the complement system by complement regulatory proteins. This study was designed to investigate the expression of complement regulatory proteins on leukemic blasts which may be susceptible to the lytic effects of the complement system in the circulation. The surface expressions of complement regulatory proteins, complement receptor 1 (CR1, CD35), decay accelerating factor (DAF, CD55), and homologous restriction factor 20 (HRF20, CD59), on peripheral blood and bone marrow blasts were evaluated by using flow cytometry in 16 acute myeloblastic leukemia (AML), 16 acute lymphoblastic leukemia (ALL), 4 chronic lymphocytic leukemia (CLL), 3 chronic myelocytic leukemia (CML) patients and control granulocytes and lymphocytes obtained from 15 healthy volunteers. mRNA expression was investigated by Northern blot analysis. mRNA abundances were calculated after normalization according to 28s rRNA. Surface expressions of CRI and DAF were marginally (p = 0.08 and p = 0.08, respectively) lower in AML, and DAF expression was significantly lower (p=0.0008) in ALL patients in comparison to their normal counterparts. Except from a slight increase that is detected for CD59 in CML patients (p=0.06), there was no significant difference between the surface expressions of CD59 in any of the groups studied. Densitometric analysis of autoradiographs obtained from Northern blots revealed that in AML patients, CR1 mRNA expression were 5.5-fold lower than controls (p=0.06), while DAF mRNA expression was significantly higher (p=0.0046). Furthermore, the mRNA expression of CRI in ALL patients was found significantly lower than in the control group (p = 0.0419). None of the values obtained from the other groups were significantly different from each other. These results suggest that leukemic blasts are protected from the lytic attack of the complement system at all levels, since all of the complement membrane regulatory proteins were expressed in all leukemia types (although at lower amounts in some cases), and it is also possible to use CRI and DAF as differentiation markers in acute leukemias.     

Effect of IL-4 on altered expression of complement activation regulators in rat pancreatic cells during severe acute pancreatitis

AIM: To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis (SAP). METHODS: SAP model of rats was established by retrograde injection of 5% sodium taurocholate (1 mL/kg) into the pancreatic duct. We immunohistochemically assayed the expression of three complement activation regulators: decay accelerating factor (DAF; CD55), 20 ku homologous restriction factor (HRF20; CD59) and membrane cofactor protein (MCP; CD46), in the pancreatic acinar cells of rats at 0, 3, 6, 12, and 24 h after the induction of SAP model. Meanwhile the levels of amylase and lipase were determined, and morphological examination was performed. Then, 61 rats were randomly divided into three groups. Group A (n = 21) received no treatment after the SAP model was established; group B (n = 20) was given IL-4 (8 μg/animal) intraperitoneally 0,5 h before the SAP model was established; group C (n = 20) was given IL-4 (8 μg/animal) intraperitoneally 0.5 h after the SAP model was established. Plasma amylase and lipase, extent of pancreatic necrosis and expression of complement activation regulators were investigated 6 h after the induction of SAP model. RESULTS: Three complement activation regulators were all expressed in pancreatic acinar cells. MCP was not found on the basolateral surface as reported. Contrary to the gradually increasing plasma level of amylase and lipase, expression of complement activation regulators decreased after SAP model was set up. At the same time, the severity of pancreatic necrosis was enhanced. A strong negative correlation was found between the ex- pression of MCP, DAF, CD59 in pancreatic acinar cells and the severity of pancreatic necrosis (r=-0.748, -0.827, -0.723; P＜0.01). In the second series of experiments, no matter when the treatment of IL-4 was given (before or after the induction of SAP model), the serum level of amylase or lipase was decreased and the extent of pancreatic necrosis was ameliorated significantly. Compared to SAP control group, the expression of DAF and CD59 in pancreas was reinforced when IL-4 was given before the induction of SAP model (P＜0.01, P＜0.05), but the expression of MCP was not influenced (P＞0.05). The expression of DAF was enhanced, when IL-4 was given after the induction of SAP model (P＜0.05), but the expression of CD59 and MCP did not change (P＞0.05). CONCLUSION: Complement activation regulators may participate in the pathogenesis of pancreatic inflammation. Downregulation of complement activation regulators expression may be one of the causes of pancreatic necrosis. IL-4 treatment may control SAP aggravation by enhancing expression of DAF and CD59 in pancreas and decreasing pancreatic necrosis. Moreover, DAF and CD59 may play an important role in the regulation of complement activation regulators during SAP.     

Overexpression of complement receptors and related antigens on the surface of bone marrow mast cells in patients with systemic mastocytosis

Depending on their stage of maturation and other factors, mast cell (MC) subsets differ from each other in terms of the expression of complement-associated antigens. This study analysed the expression of various complement-related cell surface antigens (CD11b/CR3, CD11c/CR4, CD35/CR1, CD55/DAF, CD59/MIRL, CD88/C5aR) on bone marrow mast cells (BMMC) in patients suffering from systemic mastocytosis (SM), other haematological diseases and non-haematological disorders (control groups). Expression of complement-associated cell surface antigens was analysed by flow cytometry. There were clear immunophenotypic differences between BMMC obtained from patients with SM and those from the control subjects: the percentage of patients expressing surface CD11c, CD35 and CD88 was significantly higher in patients with SM (76%, 100%, 54%) than in the control subjects (58%, 11%, 18%) (P < 0.05). In addition, the levels of CD11c, CD35 and CD88 expressed per MC (sites per cell) were significantly higher (P < 0.05) in SM than in the control group. Expression of the complement regulatory molecules CD55 and CD59 was detected in BMMC in all patients analysed. However, the levels of CD59 per BMMC were higher in patients with SM as compared with the control subjects, which could help to explain the formation of BMMC aggregates in the former group of individuals. Together, our results showed that BMMC in systemic mastocytosis overexpressed the cell surface membrane receptors involved in binding of complement components and complement-mediated cell activation. Whether this pathological expression of complement receptors is of pathophysiological significance remains to be determined.     

CD55 expression patterns on intestinal neuronal tissue are divergent from the brain

BACKGROUND: and objectives: In this study, we investigated how enteric plexuses protect themselves from complement mediated attack. For this purpose, the expression patterns of membrane bound complement regulatory proteins (mCRP) and their association with C3 deposition was determined. In addition, mCRP expression patterns of enteric plexuses were compared with those in the central nervous system (CNS). METHODS: Immunohistochemical stainings were performed to discriminate neuronal cells from glial cells and to detect the presence of CD46, CD55, CD59, and C3d. RNA in situ hybridisation (RISH) was used to determine the cell types that produce CD55 mRNA. RESULTS: Enteric plexuses minimally expressed CD46 whereas CD55 and CD59 were highly expressed. CD55 expression was also observed in a ring around Auerbach's plexuses which was not observed for CD46 and CD59. C3d was deposited around the plexuses but plexus cells themselves did not stain for C3d. In contrast with CNS neurones, enteric neurones were shown to express CD55 whereas enteric glial cells did not. This was confirmed with CD55 RISH. Phospholipase C mediated cleavage of CD55 demonstrated that CD55 was most likely attached to elastic fibres surrounding the plexus. Attached CD55 might protect CD55 negative glial cells from complement mediated injury during inflammatory reactions. CD55 on elastic fibres surrounding the plexuses most likely originated from enteric neuronal cells. CONCLUSION: In contrast with the CNS, enteric neurones express CD55 and enteric glial cells lack CD55 expression. CD55, produced by neuronal cells, attached to elastic fibres surrounding the plexuses is proposed to protect the CD55 negative glial cells within plexuses.