目的:研究血清可溶性CD40配体(sCD40L)和白细胞介素18(IL-18)水平与脑梗死的关系。方法:选择2012年5月~2014年12月于我院就诊的脑梗死患者70例纳入脑梗死组,同一时间段内在我院体检中心体检的70例健康志愿者纳入研究的健康组,分...目的:研究血清可溶性CD40配体(sCD40L)和白细胞介素18(IL-18)水平与脑梗死的关系。方法:选择2012年5月~2014年12月于我院就诊的脑梗死患者70例纳入脑梗死组,同一时间段内在我院体检中心体检的70例健康志愿者纳入研究的健康组,分离血清并测定sCD40L、IL-18、细胞黏附分子1(ICAM-1)、血管细胞黏附分子1(VCAM-1)、CD11b、CD18、基质金属蛋白酶(MMP)10、解聚素-金属蛋白酶17(ADAM17)、ADAMTS12的含量,分离外周血单个核细胞并测定CD40、CD40L、NLRP3、凋亡相关点样蛋白(apoptotic speck-like protein containing a caspase recruitment domain,ASC)、Caspase-1的含量。结果:脑梗死组患者血清中sCD40L、IL-18、ICAM-1、VCAM-1、CD11b、CD18、MMP10、ADAM17、ADAMTS12的含量以及外周血中CD40、CD40L、NLRP3、ASC、Caspase-1的表达量显著高于健康组(P〈0.05);脑梗死患者的神经功能缺损越严重,血清中sCD40L、IL-18的含量以及外周血中CD40、CD40L、NLRP3、ASC、Caspase-1的表达量越高(P〈0.05);sCD40L、IL-18高水平组脑梗死患者血清中ICAM-1、VCAM-1、CD11b、CD18、MMP10、ADAM17、ADAMTS-12的含量显著高于低水平组(P〈0.05)。结论:血清可溶性CD40配体和白细胞介素18水平升高与脑梗死的发生以及病情严重程度相关。展开更多
目的探讨ABCD3-I评分结合血清可溶性CD40配体(sCD40L)和血浆纤维蛋白原(Fib)检测对短暂性脑缺血发作(TIA)患者90d内发生脑梗死的预测价值。方法连续选取首次发病的TIA患者178例,随访90d,将发展为脑梗死的27例患者作为脑梗死组,未发展为...目的探讨ABCD3-I评分结合血清可溶性CD40配体(sCD40L)和血浆纤维蛋白原(Fib)检测对短暂性脑缺血发作(TIA)患者90d内发生脑梗死的预测价值。方法连续选取首次发病的TIA患者178例,随访90d,将发展为脑梗死的27例患者作为脑梗死组,未发展为脑梗死的151例患者作为对照组。入选者均进行ABCD3-I评分,采用酶联免疫吸附法检测sCD40L和Fib水平,绘制ROC曲线分析相关指标的预测价值。结果与对照组比较,脑梗死组ABCD3-I评分和sCD40L及Fib水平明显升高[(6.17±1.04)分vs (5.43±1.32)分,P=0.009;(222.00±28.75)μg/L vs (187.80±35.47)μg/L,P=0.014;(4.01±1.52)g/L vs (3.55±1.26)g/L,P=0.012]。ROC曲线分析显示,ABCD3-I评分联合sCD40L、ABCD3-I评分联合Fib、ABCD3-I评分联合sCD40L和Fib预测TIA患者90d内发展为脑梗死的曲线下面积分别为0.656(95%CI:0.586~0.732,P=0.001)、0.680(95%CI:0.615~0.745,P=0.000)和0.714(95%CI:0.654~0.774,P=0.000),均有预测价值,且ABCD3-I评分联合sCD40L和Fib的预测价值较前两者更高,其敏感性为90.1%,特异性为88.2%。结论 ABCD3-I评分联合sCD40L和Fib检测可进一步提高预测TIA患者90d内发展为脑梗死的准确率,且预测价值较高。展开更多
To observe the expression of CD40/CD40L on peripheral blood mononuclear cells (PBMC) in patients with eondyloma aeuminatum (CA), flow eytometry was employed to examine the expression of CD40 and CD40L on PMBC in 3...To observe the expression of CD40/CD40L on peripheral blood mononuclear cells (PBMC) in patients with eondyloma aeuminatum (CA), flow eytometry was employed to examine the expression of CD40 and CD40L on PMBC in 36 patients with CA and 20 healthy controls. Our results showed that mean level of CD40 expression in CA patients was significantly lower than that in the controls (6.58 %±2.74 % vs 14.81 %±6.12 %, t=5. 703, P〈0.05); the average level of CD40L in CA patients was also significantly lower than that in the controls (0.73 % ±0.54 % vs 2.67 %±2.43 %, t=3. 532, P〈0.05). Our resutls suggest that the reduced costimulatory interaction of CD40 and CD40L in CA patients may be one of the important factors responsible for the low cellular immunity.展开更多
Objectives To investigate the change and clinical significance of clopidogrel on platelet membrane CD40L in coronary artery disease patients before and after percutaneous coronary intervention(PCI). Methods 30 cases w...Objectives To investigate the change and clinical significance of clopidogrel on platelet membrane CD40L in coronary artery disease patients before and after percutaneous coronary intervention(PCI). Methods 30 cases who were diagnosis coronary artery diseases(CAD) by coronary angiography, mean age 56±9 years old. All the patients who had no antiplatelet aggregation contraindication, were treated with standard anti angina pectoris drugs. Before PCI, all the patients took clopidogrel 75 mg per day. Activated platelet membrane CD40L express rate was measured by flow cytometry before and after PCI 6 hours. Results Activated platelet membrane CD40L express rate were 3.73±2.15 and 2.46±0.90, respectively in 30 patients before and after PCI 6 hours. Activated platelet membrane CD40L express rate was significantly decrease after PCI 6 hours than that before PCI(P<0.01). Conclusions Clopidogrel has significance effect on platelet membrane CD40L in coronary artery disease patients undergoing PCI. Clopidogrel can suppression platelet activation and prevent thromboembolism event occurrence.展开更多
BACKGROUND Colorectal cancer(CRC)is often associated with elevated platelet count(>400×10^(9)/L),known as thrombocytosis.The role of CD40 ligand(CD40L),a member of the tumor necrosis factor family,is controver...BACKGROUND Colorectal cancer(CRC)is often associated with elevated platelet count(>400×10^(9)/L),known as thrombocytosis.The role of CD40 ligand(CD40L),a member of the tumor necrosis factor family,is controversial in CRC.Circulating CD40L is higher in CRC,but its relationship with disease staging and local and distant metastasis is not clear.Although most of the circulating CD40L is produced by platelets,no previous study investigated its relationship with CRC-related thrombocytosis.AIM To investigate the role of CD40L to predict the outcome of CRC and its relation to thrombocytosis.METHODS A total of 106 CRC patients and 50 age and sex-matched control subjects were enrolled for the study.Anamnestic data including comorbidities and histopathological data were collected.Laboratory measurements were performed at the time of CRC diagnosis and 1.5 mo and at least 6 mo after the surgical removal of the tumor.Plasma CD40L and thrombopoietin were measured via enzyme-linked immunosorbent assay,while plasma interleukin-6 was measured via electrochemiluminescence immunoassay.Patient follow-ups were terminated on January 31,2021.RESULTS Plasma CD40L of CRC patients was tendentiously higher,while platelet count(P=0.0479),interleukin-6(P=0.0002),and thrombopoietin(P=0.0024)levels were significantly higher as opposed to the control subjects.Twelve of the 106 CRC patients(11.3%)had thrombocytosis.Significantly higher CD40L was found in the presence of distant metastases(P=0.0055)and/or thrombocytosis(P=0.0294).A connection was found between CD40L and platelet count(P=0.0045),interleukin-6(P=0.0130),and thrombocytosis(P=0.0155).CD40L was constant with the course of CRC,and all baseline differences persisted throughout the whole study.Both pre-and postoperative elevated platelet count,CD40L,and interleukin-6 level were associated with poor overall and disease-specific survival of patients.The negative effect of CD40L and interleukin-6 on patient survival remained even after the stratification by thrombocytosis.CONCLUSION CD40L levels of CRC patients do not change with the course of the disease.The CD40L level is strongly correlated with platelet count,interleukin-6,thrombocytosis,and the presence of distant metastases.展开更多
Objectives To investigate the inhibitory effect of clopidogrel on release of soluble CD40 ligand (sCD40L) by ADP-activated platelet in patients with non-ST-segment elevation acute coronary syndromes(NSTEACS). Meth...Objectives To investigate the inhibitory effect of clopidogrel on release of soluble CD40 ligand (sCD40L) by ADP-activated platelet in patients with non-ST-segment elevation acute coronary syndromes(NSTEACS). Methods Forty-two patients with NSTEACS were treated with clopidogrel for 6 - 8 days. In order to obtain platelet rich plasma (PRP) samples, the venous blood was drawn before and after treatment, respectively. The platelets were activated by adenosine diphosphate (ADP) , thus releasing sCD40L, sCD40L levels were determined by en- zyme-linked immunosorbent assay (ELISA) at different time of the reaction. Results Plasma sCD40L concentration before treatment was (0. 199 ± 0. 155 ) ng/mL, and (0. 190 ± 0. 176) ng/mL after treatment ( P 〉 0.05 ). Before treatment the PRP sCD40L level at 20-minute of platelet activation was (4.34 ± 2.51 ) ng/mL, and decreased to (2.79 ±1.93 ) ng/mL after treatment ( P 〈 0. 001 ). The corresponding level at 40 - minute of platelet activation was (5.29 ± 3. 13 ) ng/mL before treatment and ( 2.87 ± 1.59 ) ng/mL after treatment( P 〈 0. 001 ). Conclusions Short-term clopidogrel administration might inhibit the release of sCD40L by ADP-activated platelet in patients with NSTEACS, suggesting that, in addition to its antiplatelet potency, clopidogrel may still have an anti-inflammatory effect.展开更多
Background Recently,studies have disclosed soluble CD40 ligand (sCD40L) during atherosclerosis development and plaque destabilization.The objective of the present study was to test the hypothesis that sCD40L levels ...Background Recently,studies have disclosed soluble CD40 ligand (sCD40L) during atherosclerosis development and plaque destabilization.The objective of the present study was to test the hypothesis that sCD40L levels are higher in acute coronary syndrome (ACS) patients with a greater extent of angiographic coronary involvement.Methods This cross-sectional study examined ACS patients who underwent coronary angiography by measuring their sCD40L levels.In order to estimate the serum levels of sCD40L,10 ml of peripheral venous blood was drawn within 24 hours of admission.sCD40L levels were measured using an enzyme-linked immunosorbent assay (ELISA,RapidBio,West Hills,CA,USA).Demographic data,presence of concomitant diseases,ACS characteristics,and angiographic findings were evaluated.A review of medical records and patient interviews were conducted to assess coronary risk factors.And the severity of coronary artery disease was evaluated using the Gensini score index.Results Two hundred and eighty-nine patients were included in the study,of whom 186 were male,with an average age of 64.1±10.0 years.Median sCD40L levels were 1.7 ng/ml (0.3-7.3 ng/ml) and Gensini scores were 50 (0-228).After adjusting for demographic variables and cardiovascular risk factors,the Gensini score was associated with the natural logarithm of the sCD40L level (Coefficient b=0.002,95% CI 0.000-0.003,P=0.029).Conclusion sCD40L levels were independently associated with angiographic severity of coronary artery disease in patients with ACS.展开更多
A key and limiting step in the process of human monocyte-derived dendritic cells (mDCs) for clinical use is their in vitro maturation and in vivo migration. We previously observed that CD40 signal facilitated human ...A key and limiting step in the process of human monocyte-derived dendritic cells (mDCs) for clinical use is their in vitro maturation and in vivo migration. We previously observed that CD40 signal facilitated human mDC growth and maturation. To further explore this process, mDCs generated with GM-CSF and IL-4 were co-cultured with apoptotic tumor cells for 24 hours, followed by incubating with anti-CD40 monoclonal antibody or TNF-a for 48 hours to generate mature DCs. The chemokine/chemokine receptor expression and functions of mature DCs upon various stimuli were determined. The expression of costimulatory molecules on apoptotic tumor cell-loaded mature DCs co-cultured with either anti-CD40 antibody (anti-CD40-DCs) or TNF-a (TNF-DCs) were up-regulated compared to immature DCs, consistent with the abilities of these cytokine to drive DC maturation in vitro. The mRNA levels of chemokines such as stromal cell-derived factor-1a (SDF-1a), EBV-induced molecule 1 ligand chemokine (ELC), and IFN inducible protein-10 (IP-10) in anti-CD40 activated DCs were increased and the dendritic cell-specific chemokine 1 (DC-CK1) was moderately up-regulated as compared with other mature DCs. The corresponding chemokine receptors CXCR4 and CCR7 of anti-CD40-DCs were significantly expressed. The CXCR3 expression on activated T cells stimulated by anti-CD40-DCs was also increased. Moreover, the anti-CD40-DCs had a stronger ability to stimulate T cell proliferation than any other DCs. The NF-xB activity was much higher in anti-CD40-DCs than that of TNF-DCs. These results offer further evidence of the importance of the CD40 signal in developing efficient human DC vaccines for cancer immune therapy. Cellular & Molecular Immunology.展开更多
Kawasaki disease(KD)is a medium vessel vasculitis with predilection to cause coronary artery abnormalities.KD is now the most common cause of acquired heart disease in developed countries.Thrombocytosis is consistentl...Kawasaki disease(KD)is a medium vessel vasculitis with predilection to cause coronary artery abnormalities.KD is now the most common cause of acquired heart disease in developed countries.Thrombocytosis is consistently found in patients with KD,usually in 2nd to 3rd week of illness.Thrombocytopenia has occasionally been reported in the acute phase of KD.An increase or decrease in platelet number in patients with KD was initially considered to be a benign phenomenon.However,recent literature on platelet biology in KD has suggested that platelets are not only increasing but are rather activated.This phenomenon has been found to increase the risk of thrombosis in these patients.Similarly a fall in platelet counts during acute stage of KD has also been found to be associated with increased severity of disease.In this review,we update on the current best understanding about pathogenic role of platelets in patients with KD.展开更多
CD40 and its cognate ligand (CD40L) are a pair of regulators of pro-inflammatory and immune responses. In the central nervous system (CNS), CD40 is expressed on a variety of cells, including vascular endothelial c...CD40 and its cognate ligand (CD40L) are a pair of regulators of pro-inflammatory and immune responses. In the central nervous system (CNS), CD40 is expressed on a variety of cells, including vascular endothelial cells, smooth muscle cells, astrocytes and microglia (the brain macrophages, being the most sensitive cell type to respond to CD40 ligand). Interaction between CD40 on microglia and CD40L presented by infiltrating T lymphocytes and other resident CNS cells triggers a series of intracellular signaling events that promote the production of a wide array of cytokines, chemokines and neurotoxins. Thus, both molecules serve as amplifiers of pro-inflammatory and immune responses in the CNS and constitute important molecular targets for therapeutic intervention of diseases.Cellular & Molecular Immunology. 2006;3(3):163-169.展开更多
文摘目的:研究血清可溶性CD40配体(sCD40L)和白细胞介素18(IL-18)水平与脑梗死的关系。方法:选择2012年5月~2014年12月于我院就诊的脑梗死患者70例纳入脑梗死组,同一时间段内在我院体检中心体检的70例健康志愿者纳入研究的健康组,分离血清并测定sCD40L、IL-18、细胞黏附分子1(ICAM-1)、血管细胞黏附分子1(VCAM-1)、CD11b、CD18、基质金属蛋白酶(MMP)10、解聚素-金属蛋白酶17(ADAM17)、ADAMTS12的含量,分离外周血单个核细胞并测定CD40、CD40L、NLRP3、凋亡相关点样蛋白(apoptotic speck-like protein containing a caspase recruitment domain,ASC)、Caspase-1的含量。结果:脑梗死组患者血清中sCD40L、IL-18、ICAM-1、VCAM-1、CD11b、CD18、MMP10、ADAM17、ADAMTS12的含量以及外周血中CD40、CD40L、NLRP3、ASC、Caspase-1的表达量显著高于健康组(P〈0.05);脑梗死患者的神经功能缺损越严重,血清中sCD40L、IL-18的含量以及外周血中CD40、CD40L、NLRP3、ASC、Caspase-1的表达量越高(P〈0.05);sCD40L、IL-18高水平组脑梗死患者血清中ICAM-1、VCAM-1、CD11b、CD18、MMP10、ADAM17、ADAMTS-12的含量显著高于低水平组(P〈0.05)。结论:血清可溶性CD40配体和白细胞介素18水平升高与脑梗死的发生以及病情严重程度相关。
文摘目的探讨ABCD3-I评分结合血清可溶性CD40配体(sCD40L)和血浆纤维蛋白原(Fib)检测对短暂性脑缺血发作(TIA)患者90d内发生脑梗死的预测价值。方法连续选取首次发病的TIA患者178例,随访90d,将发展为脑梗死的27例患者作为脑梗死组,未发展为脑梗死的151例患者作为对照组。入选者均进行ABCD3-I评分,采用酶联免疫吸附法检测sCD40L和Fib水平,绘制ROC曲线分析相关指标的预测价值。结果与对照组比较,脑梗死组ABCD3-I评分和sCD40L及Fib水平明显升高[(6.17±1.04)分vs (5.43±1.32)分,P=0.009;(222.00±28.75)μg/L vs (187.80±35.47)μg/L,P=0.014;(4.01±1.52)g/L vs (3.55±1.26)g/L,P=0.012]。ROC曲线分析显示,ABCD3-I评分联合sCD40L、ABCD3-I评分联合Fib、ABCD3-I评分联合sCD40L和Fib预测TIA患者90d内发展为脑梗死的曲线下面积分别为0.656(95%CI:0.586~0.732,P=0.001)、0.680(95%CI:0.615~0.745,P=0.000)和0.714(95%CI:0.654~0.774,P=0.000),均有预测价值,且ABCD3-I评分联合sCD40L和Fib的预测价值较前两者更高,其敏感性为90.1%,特异性为88.2%。结论 ABCD3-I评分联合sCD40L和Fib检测可进一步提高预测TIA患者90d内发展为脑梗死的准确率,且预测价值较高。
文摘To observe the expression of CD40/CD40L on peripheral blood mononuclear cells (PBMC) in patients with eondyloma aeuminatum (CA), flow eytometry was employed to examine the expression of CD40 and CD40L on PMBC in 36 patients with CA and 20 healthy controls. Our results showed that mean level of CD40 expression in CA patients was significantly lower than that in the controls (6.58 %±2.74 % vs 14.81 %±6.12 %, t=5. 703, P〈0.05); the average level of CD40L in CA patients was also significantly lower than that in the controls (0.73 % ±0.54 % vs 2.67 %±2.43 %, t=3. 532, P〈0.05). Our resutls suggest that the reduced costimulatory interaction of CD40 and CD40L in CA patients may be one of the important factors responsible for the low cellular immunity.
文摘Objectives To investigate the change and clinical significance of clopidogrel on platelet membrane CD40L in coronary artery disease patients before and after percutaneous coronary intervention(PCI). Methods 30 cases who were diagnosis coronary artery diseases(CAD) by coronary angiography, mean age 56±9 years old. All the patients who had no antiplatelet aggregation contraindication, were treated with standard anti angina pectoris drugs. Before PCI, all the patients took clopidogrel 75 mg per day. Activated platelet membrane CD40L express rate was measured by flow cytometry before and after PCI 6 hours. Results Activated platelet membrane CD40L express rate were 3.73±2.15 and 2.46±0.90, respectively in 30 patients before and after PCI 6 hours. Activated platelet membrane CD40L express rate was significantly decrease after PCI 6 hours than that before PCI(P<0.01). Conclusions Clopidogrel has significance effect on platelet membrane CD40L in coronary artery disease patients undergoing PCI. Clopidogrel can suppression platelet activation and prevent thromboembolism event occurrence.
基金Supported by the National Research,Development and Innovation Office,No.K-116128the New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research,Development and Innovation Fund,No.UNKP-20-4-I.
文摘BACKGROUND Colorectal cancer(CRC)is often associated with elevated platelet count(>400×10^(9)/L),known as thrombocytosis.The role of CD40 ligand(CD40L),a member of the tumor necrosis factor family,is controversial in CRC.Circulating CD40L is higher in CRC,but its relationship with disease staging and local and distant metastasis is not clear.Although most of the circulating CD40L is produced by platelets,no previous study investigated its relationship with CRC-related thrombocytosis.AIM To investigate the role of CD40L to predict the outcome of CRC and its relation to thrombocytosis.METHODS A total of 106 CRC patients and 50 age and sex-matched control subjects were enrolled for the study.Anamnestic data including comorbidities and histopathological data were collected.Laboratory measurements were performed at the time of CRC diagnosis and 1.5 mo and at least 6 mo after the surgical removal of the tumor.Plasma CD40L and thrombopoietin were measured via enzyme-linked immunosorbent assay,while plasma interleukin-6 was measured via electrochemiluminescence immunoassay.Patient follow-ups were terminated on January 31,2021.RESULTS Plasma CD40L of CRC patients was tendentiously higher,while platelet count(P=0.0479),interleukin-6(P=0.0002),and thrombopoietin(P=0.0024)levels were significantly higher as opposed to the control subjects.Twelve of the 106 CRC patients(11.3%)had thrombocytosis.Significantly higher CD40L was found in the presence of distant metastases(P=0.0055)and/or thrombocytosis(P=0.0294).A connection was found between CD40L and platelet count(P=0.0045),interleukin-6(P=0.0130),and thrombocytosis(P=0.0155).CD40L was constant with the course of CRC,and all baseline differences persisted throughout the whole study.Both pre-and postoperative elevated platelet count,CD40L,and interleukin-6 level were associated with poor overall and disease-specific survival of patients.The negative effect of CD40L and interleukin-6 on patient survival remained even after the stratification by thrombocytosis.CONCLUSION CD40L levels of CRC patients do not change with the course of the disease.The CD40L level is strongly correlated with platelet count,interleukin-6,thrombocytosis,and the presence of distant metastases.
文摘Objectives To investigate the inhibitory effect of clopidogrel on release of soluble CD40 ligand (sCD40L) by ADP-activated platelet in patients with non-ST-segment elevation acute coronary syndromes(NSTEACS). Methods Forty-two patients with NSTEACS were treated with clopidogrel for 6 - 8 days. In order to obtain platelet rich plasma (PRP) samples, the venous blood was drawn before and after treatment, respectively. The platelets were activated by adenosine diphosphate (ADP) , thus releasing sCD40L, sCD40L levels were determined by en- zyme-linked immunosorbent assay (ELISA) at different time of the reaction. Results Plasma sCD40L concentration before treatment was (0. 199 ± 0. 155 ) ng/mL, and (0. 190 ± 0. 176) ng/mL after treatment ( P 〉 0.05 ). Before treatment the PRP sCD40L level at 20-minute of platelet activation was (4.34 ± 2.51 ) ng/mL, and decreased to (2.79 ±1.93 ) ng/mL after treatment ( P 〈 0. 001 ). The corresponding level at 40 - minute of platelet activation was (5.29 ± 3. 13 ) ng/mL before treatment and ( 2.87 ± 1.59 ) ng/mL after treatment( P 〈 0. 001 ). Conclusions Short-term clopidogrel administration might inhibit the release of sCD40L by ADP-activated platelet in patients with NSTEACS, suggesting that, in addition to its antiplatelet potency, clopidogrel may still have an anti-inflammatory effect.
文摘Background Recently,studies have disclosed soluble CD40 ligand (sCD40L) during atherosclerosis development and plaque destabilization.The objective of the present study was to test the hypothesis that sCD40L levels are higher in acute coronary syndrome (ACS) patients with a greater extent of angiographic coronary involvement.Methods This cross-sectional study examined ACS patients who underwent coronary angiography by measuring their sCD40L levels.In order to estimate the serum levels of sCD40L,10 ml of peripheral venous blood was drawn within 24 hours of admission.sCD40L levels were measured using an enzyme-linked immunosorbent assay (ELISA,RapidBio,West Hills,CA,USA).Demographic data,presence of concomitant diseases,ACS characteristics,and angiographic findings were evaluated.A review of medical records and patient interviews were conducted to assess coronary risk factors.And the severity of coronary artery disease was evaluated using the Gensini score index.Results Two hundred and eighty-nine patients were included in the study,of whom 186 were male,with an average age of 64.1±10.0 years.Median sCD40L levels were 1.7 ng/ml (0.3-7.3 ng/ml) and Gensini scores were 50 (0-228).After adjusting for demographic variables and cardiovascular risk factors,the Gensini score was associated with the natural logarithm of the sCD40L level (Coefficient b=0.002,95% CI 0.000-0.003,P=0.029).Conclusion sCD40L levels were independently associated with angiographic severity of coronary artery disease in patients with ACS.
基金the National Natural Science Foundation of China (No 30330540 and No 30572120) by Ministry of Science and Technology of China 973 Basic Science Project 2007CB512402 863 Basic Science Project 2006AA02A254.
文摘A key and limiting step in the process of human monocyte-derived dendritic cells (mDCs) for clinical use is their in vitro maturation and in vivo migration. We previously observed that CD40 signal facilitated human mDC growth and maturation. To further explore this process, mDCs generated with GM-CSF and IL-4 were co-cultured with apoptotic tumor cells for 24 hours, followed by incubating with anti-CD40 monoclonal antibody or TNF-a for 48 hours to generate mature DCs. The chemokine/chemokine receptor expression and functions of mature DCs upon various stimuli were determined. The expression of costimulatory molecules on apoptotic tumor cell-loaded mature DCs co-cultured with either anti-CD40 antibody (anti-CD40-DCs) or TNF-a (TNF-DCs) were up-regulated compared to immature DCs, consistent with the abilities of these cytokine to drive DC maturation in vitro. The mRNA levels of chemokines such as stromal cell-derived factor-1a (SDF-1a), EBV-induced molecule 1 ligand chemokine (ELC), and IFN inducible protein-10 (IP-10) in anti-CD40 activated DCs were increased and the dendritic cell-specific chemokine 1 (DC-CK1) was moderately up-regulated as compared with other mature DCs. The corresponding chemokine receptors CXCR4 and CCR7 of anti-CD40-DCs were significantly expressed. The CXCR3 expression on activated T cells stimulated by anti-CD40-DCs was also increased. Moreover, the anti-CD40-DCs had a stronger ability to stimulate T cell proliferation than any other DCs. The NF-xB activity was much higher in anti-CD40-DCs than that of TNF-DCs. These results offer further evidence of the importance of the CD40 signal in developing efficient human DC vaccines for cancer immune therapy. Cellular & Molecular Immunology.
文摘Kawasaki disease(KD)is a medium vessel vasculitis with predilection to cause coronary artery abnormalities.KD is now the most common cause of acquired heart disease in developed countries.Thrombocytosis is consistently found in patients with KD,usually in 2nd to 3rd week of illness.Thrombocytopenia has occasionally been reported in the acute phase of KD.An increase or decrease in platelet number in patients with KD was initially considered to be a benign phenomenon.However,recent literature on platelet biology in KD has suggested that platelets are not only increasing but are rather activated.This phenomenon has been found to increase the risk of thrombosis in these patients.Similarly a fall in platelet counts during acute stage of KD has also been found to be associated with increased severity of disease.In this review,we update on the current best understanding about pathogenic role of platelets in patients with KD.
文摘CD40 and its cognate ligand (CD40L) are a pair of regulators of pro-inflammatory and immune responses. In the central nervous system (CNS), CD40 is expressed on a variety of cells, including vascular endothelial cells, smooth muscle cells, astrocytes and microglia (the brain macrophages, being the most sensitive cell type to respond to CD40 ligand). Interaction between CD40 on microglia and CD40L presented by infiltrating T lymphocytes and other resident CNS cells triggers a series of intracellular signaling events that promote the production of a wide array of cytokines, chemokines and neurotoxins. Thus, both molecules serve as amplifiers of pro-inflammatory and immune responses in the CNS and constitute important molecular targets for therapeutic intervention of diseases.Cellular & Molecular Immunology. 2006;3(3):163-169.