妊娠高血压综合征胎盘中病理相关基因的表达改变

目的研究与细胞因子信号转导等相关的病理基因在妊娠高血压综合征(妊高征)胎盘组织中的表达变化.方法采用分别包含220余种人类细胞因子相关基因或人类环境激素相关基因cDNA片段的基因芯片,检测严格配伍的正常和妊高征胎盘组织中基因表达谱的差异.结果一些疾病相关基因(GenBank:U82828、X15183)在妊高征患者胎盘中的表达高于正常,另外一些与基因表达调控有关的转录因子基因(GenBank:AL022312、M15990、U15009、L49380等)也表达增强.此外,妊高征胎盘中与细胞因子信号转导有关的大多数受体/激酶表达增强,例如GenBank登录号为M76125、U73531、L76191、L06139、AF035121、M23379、U43195等基因.结论细胞因子信号转导相关基因等的表达增强提示细胞因子的功能活跃,进一步说明胎盘局部细胞因子水平的变化与妊高征的病理发生密切相关.     

Splenocyte response to T cell-derived cytokines in thymectomized Xenopus.

A miniaturized, “hanging-drop” bioassay reveals that splenocytes from earlythymectomized (Tx) Xenopus can respond (by enhanced thymidine incorporation) to thymicdependent “cytokines” generated in PHA- or alloantigen-stimulated cultures. Preliminary evidence, using fluorescence activated cell sorting, indicates that surface IgM⁻ splenocytes, rather than sIgM⁺ cells, from Tx toads are sensitive to the crude, splenocyte-derived, active supernatants. Although these responsive cells display residual, but low, reactivity to PHA, their thymus independence is suggested by flow cytometric observations using the anti-T cell monoclonal antibody XT-1. The development of “T-like” cells in Tx Xenopus is discussed.     

Yellow fever virus strains Asibi and 17D-204 infect human umbilical cord endothelial cells and induce novel changes in gene expression

Yellow fever (YF) is a zoonotic infection with more than 200,000 cases reported annually. Relatively little is known about YF pathogenesis in humans. In this study, we demonstrate that human vascular endothelial cells are susceptible to infection with wild-type and vaccine strains of the YFV and that these infections lead to a differential cellular response to infection. The infection of endothelial cells with either virus resulted in a significant induction of interferon-inducible genes p 78 and Cig 5 while wild-type virus induced a much more pronounced IL 6 and Bc l2 response than did the vaccine strain. Both viruses induced RANTES gene expression, but only the wild-type virus had corresponding increases in RANTES protein expression. The results demonstrate that the wild-type and vaccine strains of YFV elicit significantly different responses to infection in endothelial cells, despite being nearly identical genetically. These differences may account for the attenuated phenotype of the YFV vaccine strain, though the mechanism remains unclear. These data also point to a role for vascular endothelial cells in YF hemorrhagic fever and also suggest that IL 6 may play a role in increased viral pathogenesis, perhaps by influencing coagulation via release of coagulation co-factors such as fibrin or fibrinogen.     

Physical activity and plasma interleukin-6 in humans – effect of intensity of exercise

The present study included data from three marathon races to investigate the hypothesis that a relationship exists between running intensity and elevated concentrations of interleukin (IL)-6 in plasma. The study included a total of 53 subjects whose mean age was 30.6 [95% confidence interval (CI) 1.4] years, mean body mass 77.7 (95%CI 2.0) kg, mean maximal oxygen uptake (V˙O_2max) 59.3 (95%CI 1.4) ml · min⁻¹ · kg⁻¹, and who had participated in the Copenhagen Marathons of 1996, 1997 or 1998, achieving a mean running time of 206 (95%CI 7) min. Running intensity was calculated as running speed divided by V˙O_2max. The concentration of IL-6 in plasma peaked immediately after the run. There was a negative correlation between peak IL-6 concentration and running time (r=−0.30, P < 0.05) and a positive correlation between peak IL-6 concentration and running intensity (r=0.32, P < 0.05). The IL-1 receptor antagonist (IL-1ra) plasma concentration peaked 1.5 h after the run and there was a positive correlation between the peak plasma concentrations of IL-6 and IL-1ra (r=0.39, P < 0.01). Creatine kinase (CK) plasma concentration peaked on the 1st day after the run, but no association was found between peak concentrations of IL-6 and CK. In conclusion, the results confirmed the hypothesized association between plasma IL-6 concentration and running intensity, but did not confirm the previous finding of a connection between IL-6 plasma concentration and muscle damage. Accepted: 6 August 2000     

Human cytomegalovirus infection in foci of Langerhans cell histiocytosis

 Langerhans cell histiocytosis (LCH) has been thought to be a disorder of immune regulation, and increasingly, evidence showing that the tissue damage in LCH involves lymphokines and pro-inflammatory cytokines is reported. We detected human cytomegalovirus (HCMV)-DNA in LCH cells in the foci of LCH lesions by immunohistochemistry, in situ hybridization and PCR. HCMV was detected in the nuclei and/or cytoplasm of LCH cells in 9 of 27 LCH cases by immunostaining. HCMV was probably an early antigen. In situ hybridization revealed signals for HCMV-DNA only in the nuclei of LCH cells in 10 of the 27 LCH cases. PCR analysis was performed in 20 of the LCH cases, and HCMV-DNA was detected in 7 of these. All 7 positive cases were also positive for HCMV by ISH and IHC. These findings suggested that early phase infection or reactivation of HCMV occurred in the LCH lesions. HCMV infection may be accompanied by impaired cytokine production. Our study also suggested a relationship between HCMV infection and expression of TNFα. In tissues affected by LCH, dermatopathic lymphadenopathy or malignant fibrous histiocytoma and in normal tissues no signals for Epstein-Barr virus-RNA were detected. These findings suggest that in some cases LCH is associated with HCMV infection. Received: 24 November 1998 / Accepted: 24 April 1998     

移植物细胞因子表达与小肠移植排斥反应相关性的实验和临床病例研究

目的结合移植物细胞因子表达的实验和临床病例研究，探索早期诊断小肠移植急性排斥反应的细胞因子相关的敏感指标。方法①两例短肠综合症患者接受活体小肠移植术。定期或病情变化时随时行内镜组织学检查并测定受体大鼠移植物sIL-2R、IL-4、IL-6和IFN-γ表达水平。②BN-LEW大鼠部分小肠移植，A组：SBT（n=20）；B组：SBT＋FK506（2．5mg／kg，n=20），术后第1、4、7、14和30天测定受体大鼠移植物sIL-2R、IL-4、IL-6和IFN-γ水平同时取移植肠黏膜行病理组织学检查。结果首例术后67d发生排斥反应，第2例于术后20d和80d分别发生强烈排斥反应。发生排斥反应相应时相均发生IL-2Rα、IFN-γ表达的显著升高，排斥反应控制后IL-2Rα迅速恢复，但IFN-γ仍在较高水平维持较长时间。A组大鼠术后第1天始即显示IL-2Rα、IFN-γ和IL-6表达的显著升高，于术后7d达到最高，移植后14d仍在高水平。B组仅术后第1天出现IL-2Rα、IFN-γ和IL-6表达的迅速升高，第4天已恢复至基本正常。结论移植物IL-2Rα、IFN-γ表达的升高与小肠移植急性排斥反应密切相关，有望成为早期诊断小肠移植急性排斥反应的敏感指标。     

Mouse macrophage development in the absence of the common γ chain: defining receptor complexes responsible for IL-4 and IL-13 signaling

The common γ chain (γ_c) forms a critical component of the receptors for interleukins (IL)-2, IL-4, IL-7, IL-9, and IL-15. We analyzed γ_c-deficient mice to define a role for γ_c signaling in the development and function of the macrophage lineage. No major differences in absolute cell numbers, cell surface phenotype, or in vitro function of γ^?_c compared to γ⁺_c macrophages were observed. We therefore conclude that signaling through the γ_c chain is not essential for the differentiation of mouse macrophages. Although B and T cells require γ_c for IL-4 responses, IL-4 up-regulated major histocompatibility class II molecules and inhibited nitric oxide production from γ^?_c macrophages following stimulation with lipopolysaccharide and interferon-γ. γ^?_c macrophages could also respond to IL-13, consistent with the model of a type II IL-4 receptor α/IL-13R which can function in the absence of γ_c. Both IL-4 and IL-13 responses could be completely inhibited with the mouse IL-4 antagonist QY, suggesting that all of the observed IL-13 responses pass through the type II receptor, making it the primary signaling receptor complex for IL-13 in mouse macrophages.     

JM细胞培养上清对人B淋巴细胞和小鼠脾细胞增殖的免疫调节作用

JM 是来自人胸腺不成熟 T 细胞的急性淋巴细胞白血病细胞系.本文以 SAC 刺激的人外周血纯化 B 淋巴细胞和小鼠脾细胞增殖为模型,观察了 JM 细胞培养上清(SPN_(JM))对人 B 淋巴细胞和小鼠脾细胞增殖的免疫调节作用.发现具有 T 细胞抑制活性的 SPN_(JM)对人和小鼠 B 淋巴细胞的增殖具有促进作用。在无 SAC 诱导时,SPN_(JM)与 HrIL—2协同对 B 细胞仍有促增殖作用.本实验还发现,高浓度时对 T 细胞具有抑制作用的 SPN_(JM),在低浓度时(1:640)对 T 细胞增殖亦具有促进作用.     

Is there a role of taurine bromamine in inflammation? Interactive effects with nitrite and hydrogen peroxide

Objective and Design: The myeloperoxidase system of neutrophils generates chlorinating and brominating oxidants in vivo. The major haloamines of the system are taurine chloramine (TauCl) and taurine bromamine (TauBr). It has been demonstrated in vitro that TauCl exerts both antiinflammatory and anti-bacterial properties. Much less is known about TauBr. The present study was conducted to compare bactericidal and immunoregulatory capacity of TauBr with that of the major chlorinating oxidants: HOCl and TauCl. Moreover, the effect of nitrites and H₂O₂ on TauBr activity was investigated.Materials: TauBr was prepared by reaction of HOBr with taurine. The reaction was monitored by UV absorption spectra.Methods: Bactericidal activity of TauBr, TauCl and HOCl was tested by incubation of E. coli with the compounds and determined by the pour-plate method. To test the anti-inflammatory activity the compounds were incubated with LPS and IFN- stimulated murine peritoneal macrophages. The production of following mediators was measured: nitrites by Griess reaction; TNF-, IL-6, IL-10, IL-12p40 using capture ELISA. In some experiments the compounds were incubated with either nitrites or H₂O₂.Results: In our experimental set-up TauBr and HOCl exerted strong bactericidal effects on E. coli (MBC = 110 M and 8 M, respectively), while TauCl (< 1000 M) did not kill test bacteria. However, both, TauBr and TauCl, at noncytotoxic concentrations (< 300 M) inhibited the cytokine and nitric oxide production by macrophages. H₂O₂ completely abolished the biological activities of TauBr but not those of TauCl. Nitrites did not affect any activity of TauBr or TauCl while they diminished the HOCl^– mediated bacterial killing.Conclusion: TauBr, despite very low concentration of Br^– in body fluids, may support TauCl and HOCl in the regulation of inflammatory response and in killing of bacteria by neutrophils. However, TauBr activity in vivo will depend on the presence of H₂O₂ and possible other mediators of inflammation which can compete with target molecules for TauBr.Received 16 August 2004; returned for revision 16 September 2004; accepted by A. Falus 13 October 2004