模式识别受体及其相关分子佐剂研究进展

综述了模式识别受体（Pattern recognition receptors,PRRs）及其相关分子佐剂的研究进展。PRRs是一类表达于固有免疫细胞并可识别病原体相关分子模式的识别分子。PRRs主要包括Toll样受体、NOD样受体、RIG—I样受体、清道夫受体、甘露糖受体和髓系细胞触发受体等。与PRRs直接相关的分子佐剂主要包括TLR激动剂、NLR激动剂、RIG—I和MDA5激动剂及CD40和肿瘤坏死因子受体超家族（TNFRSF）激动剂等。     

Enhancement of spinosad toxicity to<Emphasis Type="Italic">Cydia pomonella</Emphasis> neonates by monosodium glutamate receptor agonist

Recently, we reported that monosodium glutamate (MSG) is a feeding stimulant and an enhancer of pesticide toxicity against neonates of the codling moth. Herein, we show that a MSG alternative,trans-1-aminocyclobutane-1,3-dicarboxylic acid (trans-ACBD), alone or in the presence of spinosad (Success®), increases leaf tissue consumption by codling moth neonates. In contrast to MSG,trans-ACBD maintains its feeding stimulatory properties in the field even after 20 mm of simulated rain, and effectively increases spinosad efficacy in both laboratory and field experiments.     

Comparative analysis of neonicotinoid binding to insect membranes: I. A structure-activity study of the mode of [3H]imidacloprid displacement in Myzus persicae and Aphis craccivora

Neonicotinoids bind selectively to insect nicotinic acetylcholine receptors with nanomolar affinity to act as potent insecticides. While the members of the neonicotinoid class have many structural features in common, it is not known whether they also share the same mode of binding to the target receptor. Previous competition studies with [3H]imidacloprid, the first commercialised neonicotinoid, indicated that thiamethoxam, representing a novel structural sub-class, may bind in a different way from that of other neonicotinoids. In the present work we analysed the mode of [3H]imidacloprid displacement by established neonicotinoids and newly synthesized analogues in the aphids Myzus persicae Sulzer and Aphis craccivora Koch. We found two classes of neonicotinoids with distinct modes of interference with [3H]imidacloprid, described as direct competitive inhibition and non-competitive inhibition, respectively. Competitive neonicotinoids were acetamiprid, nitenpyram, thiacloprid, clothianidin and nithiazine, whereas thiamethoxam and the N-methyl analogues of imidacloprid and clothianidin showed non-competitive inhibition. The chloropyridine or chlorothiazole heterocycles, the polar pharmacophore parts, such as nitroimino, cyanoimino and nitromethylene, and the cyclic or acyclic structure of the pharmacophore were not relevant for the mode of inhibition. Consensus structural features of the neonicotinoids were defined for the two mechanisms of interaction with [3H]imidacloprid binding. Furthermore, two sub-classes of non-competitive inhibitors can be discriminated on the basis of their Hill coefficients for imidacloprid displacement. We conclude from the present data that the direct competitors share the binding site with imidacloprid, whereas non-competitive compounds, like thiamethoxam, bind to a different site or in a different mode.     

Comparative analysis of neonicotinoid binding to insect membranes: II. An unusual high affinity site for [3H]thiamethoxam in Myzus persicae and Aphis craccivora

Neonicotinoids represent a class of insect-selective ligands of nicotinic acetylcholine receptors. Imidacloprid, the first commercially used neonicotinoid insecticide, has been studied on neuronal preparations from many insects to date. Here we report first intrinsic binding data of thiamethoxam, using membranes from Myzus persicae Sulzer and Aphis craccivora Koch. In both aphids, specific binding of [3H]thiamethoxam was sensitive to temperature, while the absolute level of non-specific binding was not affected. In M persicae, binding capacity (Bmax) for [3H]thiamethoxam was ca 450 fmol mg(-1) of protein at 22 degrees C and ca 700 fmol mg(-1) of protein at 2 degrees C. The negative effect of increased temperature was reversible and hence not due to some destructive process. The affinity for [3H]thiamethoxam was less affected by temperature: Kd was ca 11 nM at 2 degrees C and ca 15 nM at 22 degrees C. The membranes also lost binding sites for [3H]thiamethoxam during prolonged storage at room temperature, and upon freezing and thawing. In A craccivora, [3H]thiamethoxam was bound with a capacity of ca 1000 fmol mg(-1) protein and an affinity of ca 90 nM, as measured at 2 degrees C. Overall, the in vitro temperature sensitivity of [3H]thiamethoxam binding was in obvious contrast to the behaviour of [3H]imidacloprid studied in parallel. Moreover, the binding of [3H]thiamethoxam was inhibited by imidacloprid in a non-competitive mode, as shown with M persicae. In our view, these differences demonstrate that thiamethoxam and imidacloprid, which represent different structural sub-classes of neonicotinoids, do not share the same binding site or mode. This holds also for other neonicotinoids, as we report in a companion article.     

Innate immunity and host defense peptides in veterinary medicine

Recent years have witnessed a surge in interest directed at innate immune mechanisms. Proper conceptualization of the key elements of innate immunity, however, is still a work in progress, because most research in immunology traditionally has been focused on components of the acquired immune response. The question of why an animal stays healthy in a world filled with many dangers is perhaps as interesting as why it sometimes surrenders to disease. Consequently, studies with an increased focus on inborn mechanisms of animal host defense may help further the development of appropriate preventative and therapeutic measures in veterinary medicine. Host defense peptides (HDPs) are central effector molecules of innate immunity, and are produced by virtually all living species throughout the plant and animal kingdoms. These gene-encoded peptides play a central role in multiple, clinically relevant disease processes. Imbalances in the expression of HDPs can lead to overt pathology in different organ systems and cell types in all species studied. In addition, HDPs are an ancient group of innate chemical protectors, which are now evaluated as model molecules for the development of novel natural antibiotics and immunoregulatory compounds. This review provides an overview of HDPs and is aimed at veterinary practitioners as well as basic researchers with an interest in comparative immunology involving small and large animal species.     

Histological and sex steroid hormone receptor changes in testes of immature, mature, and aged chickens

Sex steroid hormone receptors play a central role in the regulation of reproduction in male chickens. In this work, we evaluated by histomorphometric methods and Western blot analysis changes in the number of the different cell populations and in the content of sex steroid hormone receptors in testes from immature (1.5-month-old), mature (12-month-old), and aged (48-month-old) chickens. The number of Sertoli cells, germ cells, and Leydig cells per area of testicular tissue markedly changed according to chicken age. The highest number of Sertoli and Leydig cells was found in testes of immature chickens, with a dramatic decrease in those of mature chickens; however, the number of germ cells was the highest in mature chickens in comparison with other ages. The content of androgen receptor diminished in testes of mature and aged animals in comparison with that of immature chickens. In contrast, the content of estrogen receptor alpha and progesterone receptor was higher in testes of mature animals than in other ages. Both progesterone receptor isoforms were expressed in a similar proportion in testes of immature and mature animals. Interestingly, progesterone receptor isoform A was the predominant isoform in aged animals. These results suggest that there are marked age-dependent changes in chicken testes histology and in sex steroid hormone receptors content that should contribute to sex steroid hormone actions, in this tissue throughout the lifespan of chickens.     

仔猪产肠毒素大肠杆菌F4受体研究进展

猪肠毒素大肠杆菌F4(ETEC F4)是引起1～2周龄仔猪黄、白痢最普遍、危害最大的大肠杆菌。ETEC F4能否致病,决定于猪的小肠上皮细胞有无ETEC F4受体。本文综述了ETEC F4的黏附模式,F4特异受体在猪小肠中的分布,受体的生化特性,受体编码基因的定位、克隆现状及存在的问题,并对今后F4受体的研究方向及应用前景进行了展望。     

Toll样受体研究进展

Toll-like receptors(TLRs)是存在于机体的一类重要的模式识别受体,在机体天然免疫中起着重要的作用.TLRs还是连接天然免疫和适应性免疫的桥梁.目前TLR1-9研究的较清楚和详尽.不同TLRs识别的病原体相关分子模式各不相同.TLRs介导的机体信号传导途径分为MyD88依赖性和非MyD88依赖性.多种生物TLRs已被克隆和表达,通过进化分析,脊椎动物的TLRs可被分为6大基因家族,识别相似PAMP的TLRs聚为一簇.TLRs编码序列和功能是高度保守的.     

Specific binding of bovine, ovine, caprine and equine IgG subclasses to defined types of immunoglobulin receptors in gram-positive cocci

One hundred and twenty bacterial strains were tested for non-immune binding of radiolabelled bovine, ovine, caprine and equine immunoglobulins. Bacteria possessing previously defined IgG receptors interacted in a well defined manner with purified IgG subclass immunoglobulins. Human group C and G streptococci carrying IgG receptors type III were capable of binding all IgG subclasses in the four mammalian species studied. Protein A-containing staphylococci demonstrated a restricted specificity with binding of bovine IgG1, ovine IgG1, caprine IgG1 and IgG2 as well as equine IgG(ab). Group A streptococci which can bind human IgG did not show specific reactivity. A new type of binding unrelated to the regular Fc-mediated binding was observed with equine IgG(T).The differences in specificity for IgG subclasses suggest that structures with binding capacity to streptococcal type III Fc receptors are different from staphylococcal protein A reactive sites. Inhibition experiments performed with purified immunoglobulins showed that individual IgG subclasses differed greatly in their inhibiting capacity reflecting differences in avidity.The high avidity and the broad, unrestricted immunoglobulin G reactivity of streptococcal IgG receptor type III indicate that human group C and G streptococci may provide a valuable tool for solid phase absorption of immunoglobulins from several mammalian species.     

Effects of nicotine on expression of nicotinic acetylcholine receptors in several kinds of stem cells

AIM To detect the subunits of nicotinic acetylcholine receptors (nAChRs) in stem cells and the changes of the receptors after nicotine treatment. METHODS Human embryonic stem cell line H9 and human induced pluripotent stem cells (IPSC) were cultured without feeder layer cells. Human umbilical cord mesenchymal stem cells (UCMSC) and human bone marrow mesenchymal stem cells (BMMSC) were also selected. Total RNA and protein were extracted from 4 kinds of cells after subculture, and total RNA was extracted after nicotine treatment. The mRNA and protein expression levels of the subunits of nAChRs were determined by RT-PCR, RT-qPCR and Western blot, and the expression location of the receptors was observed by cellular immunofluorescence. RESULTS The results of RT-PCR and Western blot showed that α2, α3, α4, α7, α9 and β1 subunits of nAChRs were detected in H9 cells， IPSC and UCMSC, while only α4, α7, α9 and β1 were expressed in BMMSC. After nicotine treatment, RT-qPCR results showed that α2 was significantly down-regulated in H9 and UCMSC but up-regulated in IPSC, while β2 was significantly up-regulated in BMMSC and IPSC but down-regulated in UCMSC. CONCLUSION The subunits of nAChRs expressed in embryonic stem cells and adult stem cells are different, and with the higher differentiation potential, the cells express the more types of subunits. The regulatory effect of nicotine on nAChR subunit expression in various stem cells is different, and H9 cells show high sensitivity to the effect of nicotine.