Onset of Coronary Heart Disease is Associated with HCMV Infection and Increased CD14^+CD16^+Monocytes in a Population of Weifang,China

Objective To investigate the relationship between human cytomegalovirus(HCMV)infection and peripheral blood CD14+CD16+monocytes in the pathogenesis of coronary heart disease(CHD),and to elucidate the mechanism of pathogenesis in CHD by analyzing the correlation between infection,inflammation,and CHD,to provide a basis for the prevention,evaluation,and treatment of the disease.Methods In total,192 patients with CHD were divided into three groups:latent CHD,angina pectoris,and myocardial infarction.HCMV-IgM and-IgG antibodies were assessed using ELISA;CD14+CD16+monocytes were counted using a five-type automated hematology analyzer;mononuclear cells were assessed using fluorescence-activated cell sorting;and an automatic biochemical analyzer was used to measure the levels of triglyceride,cholesterol,high-and low-density lipoprotein cholesterols,lipoprotein,hs-CRp and Hcy.Results The positive rates of HCMV-IgM and-IgG were significantly higher in the CHD groups than in the control group.HCMV infection affects lipid metabolism to promote immune and inflammatory responses.Conclusion HCMV infection has a specific correlation with the occurrence and development of CHD.The expression of CD14+CD16+mononuclear cells in the CHD group was increased accordingly and correlated with acute HCMV infection.Thus,HCMV antibody as well as peripheral blood CD14+CD16+mononuclear cells can be used to monitor the occurrence and development of CHD.

CD_(14)^+单核细胞人类白细胞抗原-DR预测脓毒症预后及指导免疫调理治疗的初步临床研究

目的 :验证 CD+ 1 4 单核细胞人类白细胞抗原 DR( HL A DR)对于评估严重脓毒症患者免疫功能的作用 ;探讨胸腺 5肽 ( TP 5 )治疗免疫抑制的有效性。方法 :符合严重脓毒症标准 ,CD+ 1 4 单核细胞 HL A DR<30 %的患者被定义为脓毒症免疫抑制和代偿性抗炎症反应综合征 ( CARS)者纳入本研究 ,并接受 1m g TP 5肌肉注射 ,1次 / d,直至 CD+ 1 4 单核细胞 HL A DR>5 0 %或死亡。在 TP 5治疗前及结束治疗时分别测量 CD+ 1 4单核细胞 HL A DR和肿瘤坏死因子α( TNFα)、白介素 6 ( IL 6 )、IL 10和 IL 13。结果 :15例患者存活 ,5例死亡。经 TP 5治疗后所有患者的 CD+ 1 4 单核细胞 HL A DR均有不同程度提高 ,但仅存活者有显著差异。所有患者细胞因子均高于健康对照 ,治疗后存活患者的 TNFα、IL 6明显下降 ;死亡者各种细胞因子变化不明显。结论 :用 CD+ 1 4 单核细胞 HL A DR鉴别脓毒症免疫抑制并指导免疫刺激治疗是安全可靠的 ,且对评估预后有重要价值 ;TP 5可能对逆转免疫抑制有效 ,但需要严格的对照治疗研究确认 ;脓毒症的免疫抑制发生和逆转与促炎 /抗炎细胞因子平衡无关 ,确切机制有待深入探讨。

血清sCD14、sCD163水平与冠状动脉粥样硬化病变程度及稳定性的相关性

目的检测可溶性CD14(sCD14)、可溶性CD163(sCD163)在冠状动脉粥样硬化(CAS)患者中的表达水平,并探讨其与CAS病变程度及稳定性的相关性。方法前瞻性选取2019年1月至2020年10月经长安医院心血管内科确诊的216例CAS患者作为观察组,选取同期体检健康人群240例作为对照组,比较现两组受检者的一般资料和sCD14、sCD163、白细胞介素-6(IL-6)水平。将观察组患者分为不稳定型心绞痛(UAP)组104例、稳定型心绞痛(SAP)组69例、急性心肌梗死(AMI)组43例,比较三组患者的Gensini积分、血清sCD14、sCD163、IL-6的表达水平;采用Pearson相关法分析CAS患者血清sCD14、sCD163与IL-6表达水平的相关性;采用受试者工作特征曲线(ROC)曲线分析血清sCD14、sCD163表达对CAS的诊断价值。结果观察组和对照组受检者的年龄、体质量指数比较差异均无统计学意义(P>0.05),而观察组患者的总胆固醇水平及男性、吸烟、高血压、糖尿病比例明显高于对照组,差异均有统计学意义(P<0.05);观察组患者的血清sCD14、sCD163、IL-6表达水平明显高于对照组,差异均有统计学意义(P<0.05);UAP组、AMI组患者血清sCD14、sCD163、IL-6表达水平及Gensini积分明显高于SAP组,AMI组又明显高于UAP组,差异均有统计学意义(P<0.05);经Pearson相关法分析结果显示,CAS患者血清sCD14与sCD163表达水平呈正相关(r=0.716,P<0.05);血清sCD14、sCD163分别与IL-6表达水平呈正相关(r=0.833、0.606,P<0.05);以血清sCD14、sCD163水平为检测变量绘制ROC曲线,sCD14诊断CAS的ROC曲线下面积为0.904(95%CI:0.877-0.931),截断值为3.60μg/mL,灵敏度为75.0%,特异性为90.4%;sCD163诊断CAS的ROC曲线下面积为0.821(95%CI:0.784-0.859),截断值为0.76μg/mL,灵敏度为71.8%,特异性为74.2%。结论血清sCD14、sCD163在CAS中呈高表达,两者有一定相关性,可作为诊断CAS的临床指标。

CD16⁺Monocyte Subsets in Patients with Total Joint Arthroplasty

Objective: There are two monocyte populations in human blood: CD14+CD16- classical monocytes and CD14+CD16+ inflammatory monocytes. CD14+CD16+ inflammatory monocytes, account for approximately 10% of the total monocytes, may be expanded in various types of inflammatory conditions. The purpose of this study was to investigate whether the expansion of the CD14+CD16+ monocyte population represents a risk factor of aseptic loosening (AL). Methods: Peripheral monocytes subsets were measured in revision patients with AL (n = 35) and in patients with stable implants (SI, n = 56). The gene profiles of TNFα, IL-1β, CD16, CD68 and TRAP5B from collected loosening periprosthetic tissues were analyzed. Results: There were no significant differences in the CD14+CD16+ monocyte populations between the SI and AL patients. The CD14+CD16+ monocytes were marginally higher in revision patients with osteolysis (n = 30), compared to patients without osteolysis (n = 5) though no statistically difference was found. There was an association between the CD14+CD16+ monocyte subpopulation and the tissue gene profiles, including IL-1β (p = 0.063), CD68 (p = 0.036), and TRAP5B (p = 0.073). Conclusion: It was demonstrated that the expansion of CD14+CD16+ monocytes reflects, to some extent, the inflammatory status of the loosening periprosthetic tissues. It is unclear if some of those SI patients (no pain and negative radiograph) who have a higher frequency of CD14+CD16+ monocytes may be at the early stage of AL. Further evaluation of CD14+CD16+ monocyte population, independently or combined with other factors, will be useful to design a risk profile for AL incidence and progression.

Cholecystokinin octapeptide inhibits the in vitro expression of CD14 in rat pulmonary interstitial macrophages induced by lipopolysaccharide

OBJECTIVE: To study the effect of cholecystokinin octapeptide (CCK-8) on lipopolysaccharide (LPS)-stimulated pulmonary interstitial macrophages (PIM) in vitro. METHODS: PIM were isolated and cultured in the presence or absence of LPS, CCK-8, proglumide (the antagonist of CCK receptors) and vehicle. The expression of membrane CD14 (mCD14) protein was assayed by flow cytometry and soluble CD14 (sCD14) in the supernatant was analyzed semi-quantitatively by Western blot. TNF-alpha in the supernatant was detected with ELISA. RESULTS: CCK-8, at concentrations of 10(-7) mol/L and 10(-6) mol/L, significantly inhibited the expression of mCD14. Release of sCD14 and TNF-alpha in the supernatant was up-regulated by LPS (1 microg/ml) but reduced by CCK-8. The effect of CCK-8 was inhibited by proglumide. CONCLUSION: CCK-8 negatively modulated several functions of LPS-stimulated PIM through CCK receptors. This may be one of the mechanisms for CCK-8 to alleviate inflammation in lung tissue during endotoxemia.

Characterization of macrophage mutants established by their resistance to LPS and cycloheximide-induced apopotic cell death

Macrophages are activated by bacterial lipopolysaccharide (LPS) to produce inflammatory cytokines such as TNF-α or reactive oxygen species such as nitric oxide or superoxide anion. However, in the presence of an inhibitor of protein synthesis, cyclohex-imide (CHX), at 10 μg/mL, LPS at 100 ng/mL induced macrophage apoptosis rapidly without producing phenotypes of activated macrophages. In order to understand the mechanism underlying LPS-induced cytotoxicity toward macrophages, we isolated mutant cells from a macrophage-like cell line, J774.1, as clones resistant against the cytotoxic effects of LPS + CHX by using a somatic cell genetics protocol. All of the mutant clones, designated as LCR mutants, showed resistance to the cell death induced by LPS + CHX as well as to that induced by higher doses of LPS alone, as did the LPS1916 mutant cell line, which had been previously established by its resistance to 100 μg/mL LPS. Characterization of the activated macrophage phenotypes revealed that these mutants showed reduced production of TNF-α and nitric oxide in response to LPS. Further analysis showed a much reduced amount of [125I]LPS-binding and lower CD14 expression on the cell surface, in spite of an adequate intracellular expression of CD14 molecules. Besides, the molecular weight of CD14 on these mutants was around 40-48 kDa, smaller than that of the wild-type JA-4 cells (around 50-55 kDa), suggesting impaired CD14 maturation in these mutants. However, expression of Toll-like receptor 4 (TLR4) and Myd 88 on the cell surface was not different between the wild type and the mutant cells. These results suggest that LCR mutants have common phenotypes of mal-expression of CD14 molecules on the macrophage cell surface, leading to not only reduced responses to LPS-mediated macrophage activation but acquisition of resistance to LPS-induced apoptotic cell death in the presence of CHX.

Lanthanum Inhibited the Binding of LPS with Monocyte and CD 14 Expression Upregulation

To investigate the effects of lanthanum chloride on binding of LPS to monocyte and CD14 expression upregulation induced by LPS,human monocytes were analyzed by flow cytometry(FCM).The results indicated that lanthanum chloride could decrease the binding rate of LPS with monocyte significantly.LPS upregulated the expression of CD14 on monocyte in a dose dependant manner,however,lanthanum chloride could inhibit the increase of CD14 expression on monocytes by halves.Cellular & Molecular Immunology. 2004;1(5):392-394.

Celastrol inhibits inflammatory factors expression in glioblastoma

Background:Glioblastoma is one of the most common primary intracranial tumors of the central nervous system in adults.Although chemotherapy is an important component of glioblastoma treatment,its effectiveness remains unsatisfactory.Due to multiple immunosuppressive mechanisms,glioblastoma immunotherapy has not been effective in treating many patients as a result of the clinical breakthroughs in the field.Therefore,the development of cancer immunotherapy relies on the understanding of how tumors interact with the immune system and the analysis of their molecular determinants.This study identified the key interactions between immune cells in the glioma microenvironment using RNA microarrays and single-cell sequencing.Methods:First,we screened differentially expressed genes in tumor and control samples from GSE29796 and GSE50161 datasets using GEO2R.All differentially expressed genes were used to perform enrichment analysis and construct protein-protein interaction topological analysis to analyze the interaction between proteins.Using single-cell RNA sequencing data from the GSE162631 database,we identified immune cell types within the glioblastoma microenvironment,and validated the hub gene expression in these cells.In addition,based on the GEPIA and TIMER databases,hub genes were investigated and compared with immune infiltration to determine differential expression.Finally,CellChat was used to visualize the gene expression distribution and cell-to-cell communication analysis of the proteins between different types of cells.Results:We found that monocytes/macrophages may communicate with each other in the tumor microenvironment through MIF-(CD74+CXCR4)and MIF-(CD74+CD44).In addition,our study indicated that celastrol has the ability to inhibit inflammatory factors expression by MIF/CD74 signaling pathway in U87 cells.Conclusion:This study improved the effectiveness of cancer immunotherapy strategies and developed new ideas for immunotherapy that can be applied to glioblastoma.

严重烧伤患者外周血单核细胞表面人白细胞DR抗原变化的初步研究

目的 :探讨烧伤后外周血单核细胞表面人白细胞 DR抗原受体 (HL A DR)的动态变化规律及意义。方法 :选取临床烧伤患者 30例 ,依据病程长短选取病程中 1～ 5个时间点静脉采血 ,以流式细胞仪测定外周血单核细胞 HL A DR的表达率 ,并根据烧伤程度分组进行分析。结果 :伤后患者外周血单核细胞 HL A DR的表达率明显降低 ,降低程度及持续时间与伤情有关 ,特重烧伤患者与中度烧伤患者〔(4.30± 1.5 0 ) %比(13.86 %± 2 .4 0 ) %〕、中度烧伤患者与轻度烧伤患者〔(13.86± 2 .4 0 ) %比 (5 8.80± 5 .6 0 ) %〕比较差异均显著(P均 <0 .0 1)。结论 :单核细胞 HL A DR的表达率是反映免疫功能的简单实用的指标。重症烧伤后免疫麻痹可持续较长时间 ,必要的免疫加强治疗有重要意义。

转录因子MafB在非小细胞肺癌中的表达及对CD14^+单核细胞分泌Ⅰ型干扰素的影响

[目的]研究非小细胞肺癌(NSCLC)患者中转录因子MafB的表达变化,并评估MafB对NSCLC患者CD14^+单核细胞分泌Ⅰ型干扰素和诱导CD4^+T细胞分化的影响。[方法]入组41例NSCLC患者(28例鳞癌和13例腺癌)和21例健康志愿者。收集外周血和支气管肺泡灌洗液(BALF),分离血浆和外周血单个核细胞(PBMC),纯化CD14^+单核细胞和CD4^+T细胞。酶联免疫吸附实验检测血浆和BALF干扰素(IFN)-α和IFN-β的水平,反转录实时定量PCR检测外周血和BALF中MafBm RNA相对表达量,Western blot检测MafB蛋白水平。利用MafBsi RNA转染CD14^+单核细胞,观察抑制MafB对CD14^+单核细胞分泌IFN-α和IFN-β的影响,检测干扰素调节因子3(IRF3)磷酸化水平。建立CD14^+单核细胞和CD4^+T细胞的直接接触和间接接触培养系统,通过ELISA法检测培养上清中IFN-γ、白细胞介素(IL)-4、IL-17和IL-21表达水平评估抑制MafB对CD14^+单核细胞调控CD4^+T细胞分化的影响。[结果]血浆IFN-α和IFN-β水平在健康志愿者和NSCLC患者之间差异无统计学意义,但肿瘤部位BALF中IFN-α(242.5±59.98pg/ml vs 282.5±45.24pg/ml,P=0.013)和IFN-β(12.40±2.81pg/ml vs 34.42±7.83pg/ml,P<0.0001)水平均显著性低于非肿瘤部位。PBMC中MafBm RNA相对表达量和蛋白水平在健康志愿者和NSCLC患者之间差异亦无统计学意义,但肿瘤部位BALF中MafB m RNA和蛋白水平则显著性高于非肿瘤部位(P<0.0001)。MafBsi RNA转染可显著性抑制CD14^+单核细胞中MafBm RNA和蛋白的表达。MafBsi RNA转染可促进CD14^+单核细胞IFN-β的分泌(16.09±5.79pg/ml vs 6.73±1.78pg/ml,P<0.0001),增加IRF3磷酸化(P<0.0001),但对IFN-α表达无明显影响(P>0.05)。而抑制NSCLC患者CD14^+单核细胞中MafB对CD14^+单核细胞和CD4^+T细胞共培养系统中IFN-γ、IL-4、IL-17和IL-21的分泌水平并无显著性影响(P>0.05)。[结论]NSCLC患者肿瘤部位过度表达的MafB可能诱导了Ⅰ型干扰素抑制,但MafB对肿瘤部位CD14^+单核细胞的免疫调控功能可能无影响。

LIGHT在低氧性肺动脉高压形成中的作用及机制

目的初步探讨LIGHT在低氧性肺动脉高压(hypoxic pulmonary hypertension,HPH)形成中的作用及其机制。方法将20只8周龄雌性C57BL/6J小鼠[体质量(17.90±0.91)g]和20只8周龄雌性LIGHT-/-C57BL/6J小鼠[体质量(17.55±0.93)g]分为4组(n=10):(1)野生小鼠常氧组(WT-C组)、(2)野生小鼠低氧组(WT-H组)、(3)LIGHT KO小鼠常氧组(LIGHT KO-C组)、(4)LIGHT KO小鼠低氧组(LIGHT KO-H组)。WT-H组和LIGHT KO-H组小鼠置于模拟6 000 m低压舱内连续低氧饲养30 d,WT-C组和LIGHT KO-C组小鼠舱外(海拔308 m)常规饲养。检测右心室收缩压(right ventricular systolic pressure,RVSP)和右心肥厚指数(right ventricular hypertrophy index,RVHI);HE染色观察肺小动脉结构;免疫组化检测LIGHT及其受体HVEM、LTβR表达;荧光定量PCR和Western blot检测肺组织LIGHT、HVEM和LTβR、IL-6的mRNA和蛋白水平。流式细胞术检测肺组织中各类炎症细胞的比例。结果与WT-C组相比,WT-H组肺组织中LIGHT的mRNA和蛋白水平均显著增高(P<0.05),WT-H组RVSP和RVHI明显升高(P<0.05),肺小动脉明显增厚;与LIGHT KO-C组相比,LIGHT KO-H组小鼠的RVSP、RVHI和肺小动脉厚度显著增加(P<0.05),但与WT-H组相比,LIGHT KO-H组的RVSP、RVHI和肺小动脉增厚程度明显降低(P<0.05)。与WT-C组相比,WT-H组LIGHT受体HVEM表达增加,LTβR表达降低,差异具有统计学意义(P<0.05)。LIGHT KO-H组与WT-H组相比,肺组织IL-6 mRNA和蛋白水平显著降低(P<0.05)。流式细胞检测发现,与WT-C组相比,WT-H组小鼠肺组织中单核细胞比例降低[(3.88±0.87)%vs(11.03±1.71)%,P<0.05],间质巨噬细胞比例升高[(15.56±2.69)%vs(8.57±2.17)%,P<0.05];与WT-H组相比,LIGHT KO-H组的肺组织单核细胞增加[(6.55±1.01)%vs(3.88±0.87)%,P<0.05],而间质巨噬细胞的比例降低[(10.87±1.68)%vs.(15.56±2.69)%,P<0.05]。结论慢性低氧诱导肺组织中LIGHT表达增加与HPH发病机制密切相关。LIGHT可能通过HVEM信号途径促进细胞增殖、上调肺组织IL-6表达、促进肺间质巨噬细胞产生,参与HPH的形成。

Relationship of Cell Compositions in AIIografts with Outcomes after Haploidentical Transplantation for Acquired Severe Aplastic Anemia： Effects of CD34＋ and CD14＋ Cell Doses

Background： The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell transplantation （SCT）. Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated haploidentical SCT （haplo-SCT） for patients with acquired severe aplastic anemia （SAA）. Methods： A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann-Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis. Results： A total of 126 patients （97.7%） achieved neutrophil engraftment, and 121 patients （95.7%） achieved platelet engraftment. At 100 days after transplantation, the cumulative incidence of II-IV acute graft-versus-host disease （GVHD） was 32.6%. After a median follow-up of 842 （range： 124-4110） days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14＋ （P = 0.018） and CD34＋ cells （P 〈 0.001） were associated with a successful platelet engraftment. A successthl platelet was associated with superior survival （P 〈 0.001）. No correlation of other cell components with outcomes was observed. Conclusions： These results provide evidence and explain that higher doses ofCD34＋ and CD 14＋ cells in haploidentical allografts positively affect platelet engraftment, contributing to superior survival for patients with SAA.

A Critical Role of Activin A in Maturation of Mouse Peritoneal Macrophages in vitro and in vivo

Activin A, a multifunctional factor of the transforming growth factor-beta （TGF-β） superfamily, is mainly produced by microglia and macrophages, and its anti-inflammatory and pro-inflammatory activities are both related to macrophage functions. However the direct effect of activin A on the rest macrophages in vivo remains unclear. In the present study, the results showed that activin A not only increased NO and IL-1β release, but also promoted phagocytic abilities of mouse peritoneal macrophages in vitro and in vivo, whereas it did not influence MHC Ⅰ and MHC Ⅱ expression. Moreover, we found that activin A significantly upregulated the expressions of CD14 and CD68, markers of mature macrophages, on the surface of macrophages in vitro and in vivo. These data suggest that activin A can induce primary macrophage maturation in vitro and in vivo, but may not trigger the acquired immune response via regulating expression of MHC molecules involved in presentation of antigen.

Effect of Early Intensive Insulin Therapy on Immune Function of Aged Patients with Severe Trauma

This study examined the effect of intensive insulin therapy on immune function and inflammatory factors at the early phase after severe trauma. At day 1, 3, 5, 7 after admission, subsets of CD4＋ helper T lymphocytes （Th1/Th2） and human leukocyte antigen （HLA）-DR expression on CD14＋ monocytes were flow cytometrically measured. Levels of cytokines, including tumor necrosis factor-alpha （TNF-α）, interleukin-6 （IL-6）, interleukin-10 （IL-10） and other immunity markers, such as IgA, IgG, IgM, C3, C4 and C reaction protein （CRP） were examined in two groups. The results showed that TNF-α, IL-6 and CRP levels in the intensive insulin therapy group were significantly lower than those in the conventional therapy group, whereas IL-10 levels were substantially increased after intensive insulin therapy. C3 level at day 3, 5, 7 and C4 levels at day 5, 7 were lower in the intensive therapy group than in the conventional therapy group. Th1/Th2 ratios decreased gradually over time in both groups, and were much lower at day 3, 5, 7 in intensive therapy group. There were significant differences among day 3 to day 7 after admission in HLA-DR expression in CD14＋ monocytes. It was concluded that the intensive insulin therapy could decrease pro-inflammatory cytokines and increase anti-inflammatory cytokines in the elderly suffering from severe trauma, at the same time, with complement recovery being delayed. Moreover, intensive insulin therapy promoted immune suppression and, therefore, measures need be taken to address the issue.

Prevalence and Viral Load Determination of Hepatitis B Virus among Hiv Seropositive Patients Attending Kogi State Specialist Hospital Lokoja, Kogi State

Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) share common risk factors and HBV occurs in people with HIV resulting in an increased risk for HIV/HBV co-infection. Globally, hepatitis B virus infection is of serious public health causing morbidity and mortality. The increasing incidence of liver diseases caused by HBV is emerging as a significant cause of morbidity and mortality among HIV-infected individuals. A clearer knowledge of HBV prevalence in Kogi State is important in order to educate, inform the population and control epidemics through extensive vaccination and treatment programme. The aim of this study was to determine the seroprevalence of Hepatitis B infection and to evaluate molecularly HBV infection among HIV seropositive individuals. Sera samples were obtained from 218 consented HIV participants and screened for HBsAg using the commercial membrane based rapid qualitative test kit and real-time PCR was performed using Tianlong to assay the virus quantitatively. A structured questionnaire was used to collect information on patient’s demographic variables and risk factors for HBV transmission. Overall, 17 of the participants were seropositive to HBsAg. There was a significant difference between the age distribution with (P-value = 0.006) and marital status with (P-value = 0.044). Type of marriage, occupation, place of residence and risk factors associated with HIV and HBV co-infection do not show significant differences. A total of 17 HBsAg positive samples were subjected to viral load analysis, out of which 7 were highly unsuppressed, 5 were suppressed while the remaining 5 were undetectable. This study confirmed a moderately high HIV/HBV co-infection rate (7.8%). The highly unsuppressed viral load obtained from the study is a potential risk for Hepatocellular carcinoma among the study population. Enlightenment programme on routes of virus acquisition with a view to reducing the morbidity and mortality of HIV/HBV co-infection should be intensified.

Glomerular chemokine expression and the effect of steroid and cyclophosphamide pulse therapy in human crescentic glomerulonephritis

OBJECTIVE: To study glomerular expression of C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha and beta (MIP-1alpha, MIP-1beta) and the effect of steroid and cyclophosphamide (CTX) intermittent intravenous pulse therapy on expression in patients with crescentic glomerulonephritis (CGN) to further investigate the underlying mechanism of the treatment. METHODS: Twelve patients with initial biopsy-proven CGN(2), 6 with lupus nephritis (lupus-CGN, LN-CGN) and 6 with vasculitis, (vasculitis-CGN, V-CGN) were enrolled in this study. They underwent an initial biopsy before steroid and CTX intermittent intravenous pulse therapy and were biopsied again one to three months later. Expression of MCP-1, MIP-1alpha, MIP-1beta, and CD68 in glomeruli with cellular and fibrocellular crescents were examined by immunohistochemical analysis in serial sections of renal biopsies. The effect of the pulse therapy on histopathological changes was also observed. RESULTS: Although steroid and CTX intermittent intravenous pulse therapy markedly reduced the degree of glomerular crescent formation both in LN-CGN and V-CGN, the effect of the therapy on glomerular chemokine expression was significantly different between LN-CGN and V-CGN. It was found that steroid and CTX intermittent intravenous pulse therapy reduced the expression of CD68, MCP-1, and MIP-1alpha, but had no effect on MIP-1beta in glomeruli with cellular crescents of patients with LN-CGN. In patients with V-CGN, the therapy also reduced the expression of CD68, but had no effect on MCP-1, MIP-1alpha, and MIP-1beta in glomeruli with cellular crescents. It was noted that the degree of glomerulosclerosis and tubular interstitial fibrosis increased more significantly at the second biopsy in V-CGN as compared to LN-CGN. CONCLUSIONS: The efficacy of steroid and CTX intermittent intravenous pulse therapy in CGN might be affected by reduction of glomerular chemokine expression. The different changes in glomerular expression of MCP-1 and MIP-1alpha in patients with LN-CGN and V-CGN after pulse therapy may correlate to different responses to treatment and prognosis.

Innate and adaptive immune responses that control lymph-borne viruses in the draining lymph node

The interstitial fluids in tissues are constantly drained into the lymph nodes(LNs)as lymph through afferent lymphatic vessels and from LNs into the blood through efferent lymphatics.LNs are strategically positioned and have the appropriate cellular composition to serve as sites of adaptive immune initiation against invading pathogens.However,for lymph-borne viruses,which disseminate from the entry site to other tissues through the lymphatic system,immune cells in the draining LN(dLN)also play critical roles in curbing systemic viral dissemination during primary and secondary infections.Lymph-borne viruses in tissues can be transported to dLNs as free virions in the lymph or within infected cells.Regardless of the entry mechanism,infected myeloid antigen-presenting cells,including various subtypes of dendritic cells,inflammatory monocytes,and macrophages,play a critical role in initiating the innate immune response within the dLN.This innate immune response involves cellular crosstalk between infected and bystander innate immune cells that ultimately produce type I interferons(IFN-Is)and other cytokines and recruit inflammatory monocytes and natural killer(NK)cells.IFN-I and NK cell cytotoxicity can restrict systemic viral spread during primary infections and prevent serious disease.Additionally,the memory CD8+T-cells that reside or rapidly migrate to the dLN can contribute to disease prevention during secondary viral infections.This review explores the intricate innate immune responses orchestrated within dLNs that contain primary viral infections and the role of memory CD8+T-cells following secondary infection or CD8+T-cell vaccination.