The crossroads of neuroinflammation in infectious diseases: endothelial cells and astrocytes

Homeostasis implies constant operational defence mechanisms, against both external and internal threats. Infectious agents are prominent among such threats. During infection, the host elicits the release of a vast array of molecules and numerous cell-cell interactions are triggered. These pleiomorphic mediators and cellular effects are of prime importance in the defence of the host, both in the systemic circulation and at sites of tissue injury, for example, the blood-brain barrier (BBB). Here, we focus on the interactions between the endothelium, astrocytes, and the molecules they release. Our review addresses these interactions during infectious neurological diseases of various origins, especially cerebral malaria (CM). Two novel elements of the interplay between endothelium and astrocytes, microparticles and the kynurenine pathway, will also be discussed.     

二氧化氯浸泡对双孢蘑菇褐变的抑制效应及其机理分析

以‘W2000’双孢蘑菇为试验材料,设清水(CK)和ClO2浸泡(120mg·L-1)2个处理,研究ClO2浸泡处理在低温贮藏条件下对双孢蘑菇采后品质、生理及相关酶活性的影响。结果显示:ClO2浸泡处理配合0℃低温贮藏可显著降低双孢蘑菇的呼吸强度,推迟呼吸高峰的出现时间,呼吸强度较CK降低29.2%,并使呼吸高峰推迟5d出现;同时能够有效抑制子实体多酚氧化酶(PPO)和过氧化物酶(POD)的活性,控制酚类氧化产物的积累,减缓子实体褐化进程,贮藏20d时,处理的总酚含量仅为0.81μmol/mg。另外,ClO2处理还可延缓子实体硬度的下降,保持其可溶性固形物的含量,并抑制开伞,有效延长双孢蘑菇的贮藏期。研究表明,ClO2处理+低温贮藏对双孢蘑菇具有较理想的保鲜效应,可有效保持双孢蘑菇的外观和营养品质,提高商品价值,具有一定的实际应用价值。     

Endocytosis and intracellular processing of platelet microparticles by brain endothelial cells

Platelet-derived microparticles (PMP) bind and modify the phenotype of many cell types including endothelial cells. Recently, we showed that PMP were internalized by human brain endothelial cells (HBEC). Here we intend to better characterize the internalization mechanisms of PMP and their intracellular fate. Confocal microscopy analysis of PKH67-labelled PMP distribution in HBEC showed PMP in early endosome antigen 1 positive endosomes and in LysoTracker-labelled lysosomes, confirming a role for endocytosis in PMP internalization. No fusion of calcein-loaded PMP with HBEC membranes was observed. Quantification of PMP endocytosis using flow cytometry revealed that it was partially inhibited by trypsin digestion of PMP surface proteins and by extracellular Ca(2+) chelation by EDTA, suggesting a partial role for receptor-mediated endocytosis in PMP uptake. This endocytosis was independent of endothelial receptors such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and was not increased by tumour necrosis factor stimulation of HBEC. Platelet-derived microparticle internalization was dramatically increased in the presence of decomplemented serum, suggesting a role for PMP opsonin-dependent phagocytosis. Platelet-derived microparticle uptake was greatly diminished by treatment of HBEC with cytochalasin D, an inhibitor of microfilament formation required for both phagocytosis and macropinocytosis, with methyl-β-cyclodextrin that depletes membrane cholesterol needed for macropinocytosis and with amiloride that inhibits the Na(+)/H(+) exchanger involved in macropinocytosis. In conclusion, PMP are taken up by active endocytosis in HBEC, involving mechanisms consistent with both phagocytosis and macropinocytosis. These findings identify new processes by which PMP could modify endothelial cell phenotype and functions.     

The CTLA-4 and PD-1/PD-L1 Inhibitory Pathways Independently Regulate Host Resistance to Plasmodium-induced Acute Immune Pathology

The balance between pro-inflammatory and regulatory immune responses in determining optimal T cell activation is vital for the successful resolution of microbial infections. This balance is maintained in part by the negative regulators of T cell activation, CTLA-4 and PD-1/PD-L, which dampen effector responses during chronic infections. However, their role in acute infections, such as malaria, remains less clear. In this study, we determined the contribution of CTLA-4 and PD-1/PD-L to the regulation of T cell responses during Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM) in susceptible (C57BL/6) and resistant (BALB/c) mice. We found that the expression of CTLA-4 and PD-1 on T cells correlates with the extent of pro-inflammatory responses induced during PbA infection, being higher in C57BL/6 than in BALB/c mice. Thus, ECM develops despite high levels of expression of these inhibitory receptors. However, antibody-mediated blockade of either the CTLA-4 or PD-1/PD-L1, but not the PD-1/PD-L2, pathways during PbA-infection in ECM-resistant BALB/c mice resulted in higher levels of T cell activation, enhanced IFN-γ production, increased intravascular arrest of both parasitised erythrocytes and CD8⁺ T cells to the brain, and augmented incidence of ECM. Thus, in ECM-resistant BALB/c mice, CTLA-4 and PD-1/PD-L1 represent essential, independent and non-redundant pathways for maintaining T cell homeostasis during a virulent malaria infection. Moreover, neutralisation of IFN-γ or depletion of CD8⁺ T cells during PbA infection was shown to reverse the pathologic effects of regulatory pathway blockade, highlighting that the aetiology of ECM in the BALB/c mice is similar to that in C57BL/6 mice. In summary, our results underscore the differential and complex regulation that governs immune responses to malaria parasites.     

STUDY OF THE PEPPER PEST GENUS, LANKA MAULIK, AND DESCRIPTIONS OF TWO NEW SPECIES FROM CHINA (COLEOPTERA,CHRYSOMELIDAE, ALTICINAE)

突顶跳甲属L.anka Maulik此前已知17种,分布于中国云南,台湾及日本,越南,泰国,老挝,斯里兰卡和印度,是一个典型的东洋区分布属,在印度是胡椒属植物的重要害虫.又记述2新种:栗褐突顶跳甲Lanka puncticolla Wang et Ge,sp.nov.,产自云南西双版纳;律点突顶跳甲Lanka regularia Wang et Ge,sp.nov..产自西藏墨脱.至此,该属已知种增至19种,其中中国5种.列出了全部已知种名录、产地、寄主、检索表、部分种的雄虫阳茎图,记述了新种,绘制其整体图和特征图等.新种模式标本保存于中国科学院动物研究所.     

NEW RECORD GENUS MICROCREPIS CHEN FROM CHINA, AND DESCRIPTION OF A NEW SPECIES ( COLEOPTERA, CHRYSOMELIDAE,ALTICINAE)

记述了中国1新纪录属喜山跳甲属Microcrepis Chen及1新种M.laevigata Wang et Ge,sp.nov.,模式产地为云南泸水.该属此前已记录9种,均分布于喜马拉雅山脉高海拔地区,是个典型的高山型属,我国一直无分布报道.本文给出了该属世界已知10种的名录、分布、检索表及新种记述.新种模式标本保存于中国科学院动物研究所.     

头部位移检测法动物悬尾实验仪的研制

采用红外传感、激光定位、51系列单片微机控制和记忆等技术,研制一种检测动物悬尾特性的仪器,用于药物研究中的动物悬尾实验。经30例小鼠实验证明,效果良好,该仪器为动物悬尾实验提供了一种全新的先进方法。     

种群密度和培养体积对发头裸腹溞生长和繁殖的影响

研究了不同培养密度(D1=100 ind·L-1,D2=150 ind·L-1,D3 =300 ind·L-1)和培养体积(V1 =50 mL,V2=100 mL,V3 =400 mL)对发头裸腹溞生长和生殖的影响.结果表明:在相同培养密度下,发头裸腹溞首次怀卵体长、雌体第一窝幼溞数和后代总数均随着培养体积的增大而减少,而雌体所产后代的性比(雄体∶雌体)随着培养体积的增大而增大.在相同培养体积下,雌体产出后代总数随着培养密度的增加而减少.雌体最大首次怀卵体长(0.95±0.10 mm)和最大后代总数(171.3±19.8 ind)均出现在D1V1组合,最大性比(0.54±0.05)出现在D3V2组合.培养密度和培养体积及其协同作用对发头裸腹溞雌体后代总数、后代性比均具有显著影响(P＜0.001).