The superoxide-generating NADPH oxidase: structural aspects and activation mechanism

Flavocytochrome b ₅₅₈ is the catalytic core of the respiratory-burst oxidase, an enzyme complex that catalyzes the NADPH-dependent reduction of O₂ into the superoxide anion O₂ ^- in phagocytic cells. Flavocytochrome b ₅₅₈ is anchored in the plasma membrane. It is a heterodimer that consists of a large glycoprotein gp91phox (phox for phagocyte oxidase) (β subunit) and a small protein p22phox (α subunit). The other components of the respiratory-burst oxidase are water-soluble proteins of cytosolic origin, namely p67phox, p47phox, p40phox and Rac. Upon cell stimulation, they assemble with the membrane-bound flavocytochrome b ₅₅₈ which becomes activated and generates O₂ ^-. A defect in any of the genes encoding gp91phox, p22phox, p67phox or p47phox results in chronic granulomatous disease, a genetic disorder characterized by severe and recurrent infections, illustrating the role of O₂ ^- and the derived metabolites H₂O₂ and HOCl in host defense against invading microorganisms. The electron carriers, FAD and hemes b, and the binding site for NADPH are confined to the gp91phox subunit of flavocytochrome b ₅₅₈ . The p22phox subunit serves as a docking site for the cytosolic phox proteins. This review provides an overview of current knowledge on the structural organization of the O₂ ^--generating flavocytochrome b ₅₅₈ , its kinetics, its mechanism of activation and the regulation of its biosynthesis. Homologues of gp91phox, called Nox and Duox, are present in a large variety of non-phagocytic cells. They exhibit modest O₂ ^--generating oxidase activity, and some act as proton channels. Their role in various aspects of signal transduction is currently under investigation and is briefly discussed. Received 28 May 2002; received after revision 20 June 2002; accepted 24 June 2002     

Iron metabolism in the mononuclear phagocyte system

The maintenance of body iron homeostasis requires the coordination of multiple regulatory mechanisms of iron metabolism. The mononuclear phagocyte system （MPS, composed of monocytes, macrophages, and their precursor cells） is crucial in the maintenance of iron homeostasis. Recycling of iron is carried out by specialized macrophages via engulfment of aged erythrocytes. The iron stores of macrophages depend on the levels of recovered and exported iron. However, the molecular mechanisms underlying iron homeostasis in macrophages are poorly understood. Recent studies characterizing the function and regulation of natural resistance-associated mac- rophage protein 1 （Nrampl）, divalent metal transporter 1 （DMT1）, HLA-linked hemechromatosis gene （HFE）, ferroportin 1 （FPN1）, and hepcidin are rapidly expanding our knowledge on the molecular level of MPS iron handling. These studies are deepening our under- standing about the molecular mechanism of iron homeostasis and iron-related diseases.     

鸡血清—γ球蛋白非特异性免疫功能的试验研究

我们就鸡血清γ—球蛋白的非特异性免疫功能作了探索性的研究,其中包括对补体活性、吞噬细胞功能、T—细胞和B—细胞的变化的影响.结果证明γ—球蛋白能提高补体活性,促进吞噬细胞功能,而对T细胞和B细胞的比例无明显影响.     

在仿刺参体腔液中发现新的调理素样分子

通过研究发现,仿刺参体腔液中存在一种新的调理素样分子。通过SDS-PAGE,凝胶过滤层析,质谱分析等方法进行蛋白质的纯化和分析,采用荧光显微镜观察吞噬细胞对酵母细胞的吞噬作用,发现一种分子量约为18 kDa的分子可以结合到酵母细胞表面,并可以增强吞噬细胞的吞噬作用。推测这种分子是无脊椎动物调理素样分子中的新成员。同时也发现,虽然调理素样分子能够增强吞噬细胞的吞噬作用,但是,它不是单独起作用的,仍然必须依赖体腔液中其他未知成分,而对未知成分的鉴定需要进一步研究。     

创伤弧菌触发吞噬细胞细胞骨架重排和诱导细胞凋亡的研究进展

创伤弧菌(Vibrio vulnificus,V.vulnificus)感染是一种少见而又致命性的重要疾病.由于起病急、死亡率高,创伤弧菌感染的有效预防和治疗受到严峻的挑战,促使人们对创伤弧菌的致病机制进行更为深入地研究.吞噬细胞在机体抗感染免疫中起着重要的作用.由于感染后触发宿主吞噬细胞骨架改变及诱导其凋亡是多种病原菌入侵的机制之一,与疾病的发生、发展和结局有着密切关系.本文就创伤弧菌感染后,触发吞噬细胞细胞骨架改变及诱导细胞凋亡的研究进展作一综述.     

Voltage-gated proton channels

The history of research on voltage-gated proton channels is recounted, from their proposed existence in dinoflagellates by Hastings in 1972 and their demonstration in snail neurons by Thomas and Meech in 1982 to the discovery in 2006 (after a decade of controversy) of genes that unequivocally code for proton channels. Voltage-gated proton channels are perfectly selective for protons, conduct deuterons half as well, and the conductance is strongly temperature dependent. These properties are consistent with a conduction mechanism involving hydrogen-bonded-chain transfer, in which the selectivity filter is a titratable amino acid residue. Channel opening is regulated stringently by pH such that only outward current is normally activated. Main functions of proton channels include acid extrusion from cells and charge compensation for the electrogenic activity of the phagocyte NADPH oxidase. Genetic approaches hold the promise of rapid progress in the near future.