巨噬细胞的极化与牙周炎

背景：牙周炎是发生在牙周支持组织的炎症,具体表现为牙龈的炎症及牙槽骨吸收。巨噬细胞可通过M1,M2极化在牙周炎发生发展中发挥作用,影响牙周炎的病情进展。目的：通过对巨噬细胞极化与牙周炎的关系及其相关机制进行综述,为牙周炎的临床治疗提供思路。方法：第一作者利用Pub Med和中国知网数据库检索1991-2022年发表的相关文献,以“macrophage polarization,M1/M2 macrophage”等为英文检索词,以“巨噬细胞极化、M1/M2巨噬细胞、牙周炎”等为中文检索词,阅读每篇文献的文题、摘要进行初筛,最终筛选出97篇文献进行归纳分析。结果与结论：(1)巨噬细胞作为人体固有免疫细胞,在炎症发生发展过程中起重要作用。巨噬细胞在环境刺激下会发生极化,且巨噬细胞极化是一个复杂的过程。(2)JAK/STAT、TLRs/核转录因子κB、PI3K/Akt等信号通路,炎症因子如肿瘤坏死因子α、干扰素γ、白细胞介素4和白细胞介素13等,以及表观遗传学等均可影响其极化。(3)巨噬细胞M1型极化促进炎症进展,巨噬细胞M2型极化发挥抗炎作用。(4)不同极化类型的巨噬细胞通过各种信号通路及分...     

膝骨性关节炎患者滑膜炎的发病机制及研究进展

背景：在膝骨性关节炎的发病机制研究中,逐渐认识到膝关节滑膜的炎性改变在膝骨性关节炎的发病过程中起到了重要的作用。 目的：对近15年有关膝骨关节炎中滑膜炎发病机制的研究进行归纳,并对国内外在分子生物学领域进行的实验成果进行总结。 方法：检索万方数据库、维普信息资源系统、CNKI数据库及PubMed数据库。以“骨关节炎”、“滑膜炎”、“发病机制”为关键词检索2000至2015年的文献,收集膝骨关节炎中滑膜炎发病机制研究的文献。共检索文献3 446篇,经过筛选,最终纳入36篇文献。 结果与结论：膝关节滑膜炎可能是骨关节炎的超早期表现,滑膜炎的发展可能影响骨关节炎的进展。在骨关节炎的形成过程中,滑膜的自身炎性反应及释放的炎性介质和细胞因子、蛋白对疾病的发生起到重要作用,但直到今天,在分子水平还不能对滑膜炎症的发病途径进行公认的描述。  中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

小鼠巨噬细胞极化与焦亡的关系研究

目的：探讨小鼠巨噬细胞极化与焦亡的关系。方法：RAW264.7小鼠巨噬细胞分为3组：M0组、M1组和M2组，M1组予以LPS和IFN-γ诱导，M2组予以IL-4和IL-13诱导，M0组予以等量PBS作为对照。流式细胞术检测细胞表型及焦亡，PI染色观察焦亡细胞定性，LDH检测细胞活性，ELISA检测炎症因子IL-1β、IL-18水平，RT-qPCR及Western blot检测caspase-1、caspase-11和GSDMD mRNA和蛋白水平。结果：倒置显微镜观察到极化后M1与M0、M2巨噬细胞形态差异显著；流式细胞术检测M1、M2巨噬细胞特异性分子结果证明诱导极化成功；与M0相比，M1、M2组炎症因子IL-1β、IL-18水平均升高（P<0.05）;M1组PI染色阳性率高于M0和M2组；与M0和M2相比，M1型巨噬细胞活化的caspase-1、caspase-11和GSDMD mRNA和蛋白表达增加。结论：LPS+IFN-γ和IL-4+IL-13可分别成功诱导M0型巨噬细胞向M1和M2型极化，且极化后的M1型巨噬细胞形态与M0、M2型差异显著；M0、M1和M2型巨噬细胞均可...     

骨性关节炎患者退变软骨及滑膜组织中细胞因子的表达

背景：骨性关节炎的炎症反应是由软骨细胞、滑膜组织分泌的细胞因子所介导的。关节软骨和滑膜组织内含有多种细胞因子,在关节软骨的损伤修复中起着重要的调节作用。 目的：分析软骨细胞、滑膜组织分泌的细胞因子与骨性关节炎发病的关系及影响。 方法：由第一作者应用计算机检索万方数据库(www.wanfangdata.com.cn),PubMed数据库(www.ncbi.nlm.nih.guv/pubmed)检索时间：2005至2010年。检索词为“骨性关节炎,退变,软骨组织,细胞因子”。计算机初检得到146篇文献,阅读标题和摘要进行初筛,排除因研究目的与此文无关的86篇,内容重复性的研究40篇,保留21篇骨性关节炎患者退变软骨及滑膜组织中各种细胞因子作用及影响的相关文献作进一步分析。 结果与结论：细胞因子主要是指活化的免疫细胞和某些基质细胞分泌的一类非特异调节免疫应答和介导炎症反应的小分子蛋白质,包括由淋巴细胞产生的淋巴因子,单核巨噬细胞产生的单核因子及其他细胞因子等。关节滑膜细胞分泌的细胞因子可部分解释骨性关节炎的病理过程,在炎症关节中起着重要的作用。虽然越来越多的学者重视到滑膜细胞、软骨细胞分泌细胞因子的作用,但主要是研究外源性细胞因子对软骨细胞或滑膜细胞的影响,而其内源性细胞因子在骨性关节炎发病中的作用却未广泛开展研究。     

机械应力调控Hippo通路影响骨关节炎的发生与发展

背景：骨关节炎是一种常见的由关节软骨退行性改变所导致的关节慢性炎症，越来越多的研究表明机械应力与骨关节炎的发展密切相关。Hippo通路既参与机体组织细胞发育又是机械应力的效应因子，参与调控骨代谢和软骨代谢。目的：通过调控Hippo通路可能成为干预骨关节炎的新靶点之一，因而此文通过对机械应力调控Hippo通路影响骨关节炎的研究进行综述，以期为骨关节炎的发病机制提供思路并对骨关节炎的治疗方法提供新的理论依据。方法：采用PubMed、Web of Science、Embase、中国知网、维普及万方数据库进行文献检索，检索各数据库建库至2023年有关机械应力对骨关节炎的影响及机械应力、Hippo通路与骨关节炎相关的所有文献，最终纳入75篇文献进行综述。结果与结论：(1)不同机械应力对骨关节炎的细胞增殖凋亡与分化、骨关节炎症与血管稳态发挥不同的作用；(2)坚硬细胞外基质、低细胞密度、中等剪切力、中等拉伸力及压缩力通过活化YAP/TAZ可达到细胞增殖、成骨分化、血管稳态及抑制炎症反应的作用；(3)软细胞外基质、高细胞密度、过度剪切力、过度拉伸力及压缩力通过失活YAP/TAZ进而抑制细胞增殖、促软骨...     

软骨终板干细胞外泌体活化巨噬细胞自噬抑制软骨终板炎的研究

目的 探讨软骨终板干细胞外泌体通过调控巨噬细胞进而抑制软骨终板炎的机制。方法 采用免疫组化检测炎症因子和巨噬细胞在不同分级分期退变的软骨终板组织中的表达和浸润，NTA(nanoparticle tracking analysis)和透射电镜鉴定外泌体，外泌体质谱检测和KEGG富集分析预测相关信号通路，Western blotting和免疫荧光检测巨噬细胞中自噬因子LC3A/B和炎症因子IL-1β、IL-6及TNF-α的蛋白水平。结果 在临床标本中，软骨终板的退变程度与巨噬细胞浸润数量IL-1β水平均正相关；40μg/ml软骨终板干细胞外泌体可有效活化巨噬细胞自噬，使P62表达降低，LC3B表达增加；自噬激动剂Rapamycin(20μmol/ml)则降低了TBHP诱导巨噬细胞炎症因子IL-6、IL-1β的水平。结论 软骨终板干细胞外泌体通过活化巨噬细胞自噬，降低其炎症因子表达，延缓了软骨终板炎的进程。     

早期短暂M1巨噬细胞在骨组织工程中的作用及应用

背景：早期短暂存在的M1巨噬细胞在骨组织工程材料植入后可以发挥有益作用，调控M1巨噬细胞产生早期适度炎症反应的策略研究逐渐广泛，在骨组织工程材料的设计中取得了许多研究进展。目的：综述早期短暂存在的M1巨噬细胞在骨组织工程中的作用，以及近年诱导激活早期短暂M1巨噬细胞策略在骨组织工程领域的应用研究进展。方法：检索收录在PubM ed、万方数据库、CNKI中国期刊全文数据库2012年1月至2022年10月的相关文献，以“M1，巨噬细胞，骨免疫学，骨免疫调节，骨缺损，骨再生，炎症反应，血管生成，组织工程，生物材料”为中文检索词，以“M1,macrophage,bone,osteogenesis,osteoimmunology,angiogenesis”等为英文检索词，筛选排除与研究目的无关与重复的文献，最终选取符合标准的63篇文献进行综述。结果与结论：早期短暂存在的M1巨噬细胞在骨组织工程中具有促进血管形成、促进骨髓间充质干细胞成骨分化以及促进M2表型转化的重要作用。诱导激活早期短暂M1巨噬细胞策略能够以符合早期自然骨愈合规律的方式调控局部免疫微环境进而促进骨缺损修复，策略包括通过改变骨组织...     

淫羊藿苷治疗骨性关节炎过程中对关节软骨、软骨下骨、滑膜等影响的机制

文题释义： 淫羊藿苷：为淫羊藿干燥茎叶的提取物,呈淡黄色针状结晶粉末, 相对分子质量为676.65, 属黄铜类化合物,现代药理学研究发现其具有很强的生物活性, 对骨组织、免疫系统、肿瘤组织、神经系统、生殖系统、内分泌系统和心血管系统等具有显著作用。 滑膜：是关节囊的内层。滑膜呈淡红色,平滑闪光,薄而柔润,由疏松结缔组织组成,其功能是制造和调节滑液等。滑膜直接附着于关节软骨的边缘并向内贴附在关节囊内的非关节区域,覆盖在关节囊、关节内韧带、骨与肌腱表面。滑膜分泌滑液,在关节活动中起重要作用。背景：淫羊藿苷是具有补肾强筋健骨功效的淫羊藿的主要有效成分,近年来大量的研究发现淫羊藿苷在治疗骨性关节炎方面有着显著作用。 目的：综述淫羊藿苷治疗骨性关节炎的分子机制研究进展。 方法：第一作者应用计算机以“Icariin、Osteoarthritis、Cartilage、Subchondral bone、Synovial membrane 、Synovium、Inflammation”及“淫羊藿苷、骨关节炎、骨性关节炎、软骨、软骨下骨、滑膜、炎症”作为主题词检索PubMed、中国知网、万方、维普等数据库相关文献,按入选标准及排除标准进行筛选,最终纳入42篇文献进行分析。 结果与结论：淫羊藿苷通过促进骨髓间充质干细胞的成软骨分化及增强软骨细胞和成骨细胞的增殖,抑制软骨细胞外基质的降解、降低破骨细胞的活性和减轻炎症因子所致的滑膜炎症反应来有效的治疗骨性关节炎。但其最佳有效剂量及浓度安全性仍需要大量实验研究,目前绝大部分实验仍停留在动物及组织细胞等基础实验,尚需要大量临床研究,继续完善其具体机制,以期为淫羊藿苷治疗骨关节炎提供循证医学证据。ORCID:0000-0002-2013-743X(余绍涌)中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

类风湿性关节炎滑膜组织中CD147表达的检测

目的：探讨类风湿性关节炎(RA)滑膜组织CD147的表达。方法：采用免疫组织化学SP染色，双重免疫荧光染色及激光扫描共聚焦显微镜分析检测RA患者受损关节软骨-血管翳汇合部(CPJ)滑膜组织中CD147的表达，并与骨关节炎(OA)滑膜组织CD147的检测相对照。结果：SP染色显示3例OA滑膜组织CD147的表达均为阴性，而11例RA滑膜组织中均检测到CD147的表达，表达CD147的细胞为单核-巨噬细胞、淋巴细胞和滑膜成纤维样细胞。双重免疫荧光染色及激光扫描共聚焦显微镜分析证实表达CD147的细胞为单核-巨噬细胞，中性粒细胞及T细胞。结论：RA滑膜细胞CD147的表达增高。CD147可能是导致RA受损关节软骨、骨基质降解的重要因素之一。     

谷胱甘肽过氧化物酶4介导铁死亡在膝骨关节炎滑膜炎发生发展中的作用

背景：滑膜炎在膝骨关节炎早期进展中起主导作用，是潜在的早期治疗靶点，但滑膜炎发生机制尚不清楚。在动物模型中，全身铁含量增加和细胞内铁摄取升高可诱发和加剧骨关节炎，但滑膜炎与铁死亡的关系仍不清楚，因此探讨铁死亡在骨关节炎滑膜炎发生发展中的作用需进一步研究。目的：探讨谷胱甘肽过氧化物酶4(glutathione peroxidase4,GPX4)介导的铁死亡在膝骨关节炎滑膜炎发生发展过程中的作用。方法：入选行膝关节镜或关节置换手术的骨关节炎患者43例以及行关节镜治疗半月板损伤或韧带撕裂患者10例，根据患者术前X射线平片Kellgren-Lawrence分级分为3组：对照组(KLG 0)10例，早期膝骨关节炎组(KLG 1,2)20例和晚期膝骨关节炎组(KLG 3,4)23例。采用苏木精-伊红染色观察各组滑膜炎的严重程度，普鲁士蓝染色评估各组滑膜组织中的铁沉积情况，免疫组化法检测ACSL4、GPX4、环氧化酶2、肿瘤坏死因子α在滑膜组织中的表达，Western blot和免疫荧光分别检测ACSL4、GPX4蛋白的表达。结果与结论：(1)与对照组相比，骨关节炎组滑膜组织中铁含量增加，且晚期膝骨...     

Electrolyte Levels in Neoplastic and Nonneoplastic Human Urothelium After Ouabain Treatment: X-Ray Microanalysis of Bulk Hydrated Samples

Samples of neoplastic and nonneoplastic human urothelium were immediately frozen, incubated in Krebs' saline and then frozen, or incubated in 10^-5 mol/L ouabain in Krebs' saline and then frozen. The frozen specimens were then planed in a cryoultramicrotome and examined by low-temperature scanning electron microscopy. X-Ray microanalysis was performed on the superficial urothelial cells. Neoplastic cells immediately frozen and those incubated in Krebs' saline had significantly higher K⁺/Na⁺, K⁺/P, and K⁺/Cl^- ratios and lower Na⁺/P and Cl^-/P ratios than nonneoplastic cells. Incubation in ouabain led to a fall in the K⁺/Na⁺, K⁺/P, and K⁺/Cl^- ratios and a rise in the Na⁺/P and Na⁺/Cl^- ratios in both neoplastic and nonneoplastic cells and effectively nullified the difference between them. These results are consistent with the concept that in neoplasia a primary event is stimulation of Na⁺/H⁺ exchange, which leads to secondary stimulation of the ouabain-sensitive Na⁺/K⁺ ATPase pump.     

Further evidence for infection of pigs with human-like H1N1 influenza viruses in China

Classical swine and avian-like H1N1 influenza viruses were reported widely in swine population worldwide, but human-like H1N1 swine viruses were reported occasionally. In 2006, a human-like H1N1 swine virus (A/swine/Guangdong/96/06) was isolated from pigs in Guangdong province, which was reported in China for the first time. To get further evidence for infection of pigs with human-like H1N1 influenza viruses, we analyzed eight gene segments of three human-like swine H1N1 viruses (A/swine/Guangdong/96/06, A/swine/Tianjin/01/04 and A/swine/Henan/01/06) isolated in China. All the eight genes of the three viruses are highly homologous to recent (about 2000) and early (1980s) human H1N1 influenza viruses, respectively. Phylogenetic analyses revealed that A/Swine/Guangdong/96/06 was directly derived from about 2000 human H1N1 influenza viruses, while A/swine/Tianjin/01/04 and A/swine/Henan/01/06 seemed to be descendants of human H1N1 viruses circulating in 1980s. Seroprevalence of our isolate (A/swine/Guangdong/96/06) confirmed the presence of human-like H1N1 virus in pigs in China. Existence of these influenza viruses, especially older viruses (A/swine/Tianjin/01/04 and A/swine/Henan/01/06), indicates that human-like H1N1 influenza viruses may remain invariant for long periods in pigs and provides the evidence that pigs serve as reservoirs of older influenza viruses for human pandemics.     

Variation in 5' Promoter Region of the APOE gene Contributes to Predicting Ischemic Heart Disease (IHD) in the Population at Large: the Copenhagen City Heart Study

The objective of this study was to evaluate whether an increased hazard of developing ischemic heart disease (IHD) is associated with any of the three genotypes A₅₆₀T₈₃₂/A₅₆₀T₈₃₂, A₅₆₀T₈₃₂/A₅₆₀G₈₃₂ and A₅₆₀T₈₃₂/T₅₆₀T_832, defined by variations in two non-coding SNPs in the 5' promoter region of the apolipoprotein E ( APOE) gene. These genotypes were selected because they distinguished between high and low levels of HDL-C, TG and/or T-C in our earlier study of multiple samples defined by gender and population. We found a significant increase (p<0.05) in the hazard of IHD in females with the A₅₆₀T₈₃₂/T₅₆₀T₈₃₂ genotype that remained significant after fitting the effects of dyslipidemia, other established risk factors, and the structural isoform variations of the ApoE molecule. We discuss why this statistically significant genetic predictor may not be an appropriate screening test for IHD in the Danish population at large.     

Promoter methylations of p16INK4a and p14ARF genes in early and advanced gastric cancer. Correlations of the modes of their occurrence with histologic type

The INK4a/ARF locus encodes two cell cycle-regulatory proteins, p16^INK4a and p14^ARF. These share an exon using different reading frames, and act through Rb and p53 pathways. Recently, it has been found that silencing of p16^INK4a and p14^ARF expressions by aberrant methylation of the CpG islands in the promoter regions is an alternative mechanism that inactivates possible tumor suppressor functions in various tumors. To clarify the features of gastric cancers with promoter methylation of p16^INK4a and p14^ARF, we investigated the methylation status in gastric cancer cell lines and primary gastric cancers using methylation-specific PCR (MSP), and correlated the methylation status with microsatellite instability (MSI), DNA ploidy pattern, p53 immunohistochemistry, and various clinicopathologic factors, paying attention to the correlations with the histologic types. Of 10 cell lines studied, silencing of the expression of p16^INK4a and p14^ARF due to promoter methylation was detected by MSP and RT-PCR in six (60%) and two (20%) cell lines, respectively. p14^ARF silencing was detected only in cell lines derived from gastric cancer of the diffuse type, while p16^INK4a silencing was found in cell lines derived from both diffuse and intestinal types. In 59 primary gastric cancers, promoter methylation of p16^INK4a and p14^ARF was found in 10 (17%) and 14 (24%) of the tumors independently, there being an association with DNA diploidy, but not with p53 immunohistochemistry. p16^INK4a methylation was found irrespective of tumor stages and histology. Whereas p14^ARF methylation was found more frequently in intestinal type cancers in an early stage and in diffuse type cancers in an advanced stage, MSI tended to be related especially to p14^ARF methylation in cancers of the intestinal type. Thus, the significance of p14^ARF methylation differed between intestinal and diffuse types, while such a difference was not observed in p16^INK4a methylation.     

Dengue virus-induced cytotoxin releases nitrite by spleen cells

Dengue type-2 virus (DV) infection in mice induces T cells to produce a cytokine, the cytotoxic factor (CF), which induces H2-A positive macrophages to produce another cytokine, cyotoxin (CF2), which amplifies its cytotoxic effects on target cells. The present study was undertaken to investigate the production of nitrite (NO⁻₂) by the spleen cells of mice in vitro and in vivo following inoculation of CF2. Maximum NO⁻₂ production occurred at 1 hour after inoculation of 100 μg CF2. Pretreatment of CF2 with anti-CF2-antisera (CF2-As) inhibited the production of NO⁻₂. Pretreatment of the spleen cells with N ^G-monomethyl- l -arginine (NMA) or with arginase inhibited NO⁻₂ production. The NO⁻₂ production was diminished in a dose dependent manner by treatment of spleen cells with the Ca²⁺ channel blocking drug, nifedipine and Zn²⁺ as ZnSO₄. The findings of the present study thus demonstrate that CF2 induces production of NO⁻₂ in the spleen cells in a CA²⁺-dependent manner which may be a mechanism of target cell killing.     

金刚烷胺与利巴韦林对不同甲型流感病毒株的体外作用敏感性比较

目的评价金刚烷胺和利巴韦林对不同甲型流感病毒株的体外抑制作用,为临床选择抗流感病毒药物提供实验依据。方法分别接种甲型流感病毒标准实验株[H1H1（A/PR/8/34、A/FM1/47）,H3N2（A/Aichi/2/1968）]和临床分离株[H1N1（A/Guangzhou/GIRD02/2009、A/Guangzhou/GIRD166/2009）,H3N2（A/Guangzhou/GIRD18/2009、A/Guangzhou/GIRD26/2009）],于狗肾细胞（MDCK）,采用空斑试验观察金刚烷胺和利巴韦林对甲1和甲3型流感病毒不同实验株和分离株的敏感性。对测试毒株的MP基因进行序列测定和分析,了解金刚烷胺的药物敏感性。结果金刚烷胺在MDCK细胞的半数毒性浓度（TC50）为335μg/ml,对部分甲型流感病毒标准实验株[A/FM1/47（H1N1）、A/Aichi/2/1968（H3N2）]及临床分离株[A/Guangzhou/GIRD02/2009（H1N1）]有抑制作用（半数有效浓度IC50分别为14.9、20.1、16.8μg/ml）。利巴韦林的TC50为2.05mg/ml,对测试的所有毒株均有抑制作用（IC50为6.8～37μg/ml）。金刚烷胺耐药毒株均为单位点突变（第31位的丝氨酸S置换为天冬酰胺N,S31N）。结论甲型流感病毒对金刚烷胺较易出现耐药,而利巴韦林体外对金刚烷胺敏感株和耐药株均有显著的抑制作用,临床抗流感病毒治疗时可考虑应用。     

Genetic Analysis of the Nonstructural (NS) Genes of H9N2 Chicken Influenza Viruses Isolated in China During 1998–2002

H9N2 subtype avian influenza viruses are widespread in domestic poultry. Genetic analysis indicated that three lineages of H9N2 viruses have been established in Eurasia and only one lineage is present on chicken farms in mainland China. Here, NS1 genes of eight H9N2 chicken influenza viruses, isolated in mainland China during 1998–2002, were completely sequenced and phylogenetically analyzed. By comparison, the homology of the NS1 of the A/chicken/Neimenggu/ZH/02 (Ck/NM/ZH/02) strain had a high identity (93.8%) with that of A/chicken/Korea/323/96 (Ck/Kor/323/96), which is an A/duck/Hong Kong/Y439/97 (Dk/HK/Y439/97)-like virus. NS1 peptides of seven strains possessed 217 amino acids, while that of the strain Ck/NM/ZH/02 coded 230 amino acids. Except for the amino acid at position 225, the additional amino acid sequence (13 AAs) of NS1 of Ck/NM/Zh/02 at the carboxy-terminus is identical with that of Ck/Kor/323/96. Phylogenetic analysis showed that seven of the tested strains belong to the A/duck/Hong Kong/Y280/97 (DK/HK/Y280/97)-like lineage, while the NS1 gene of Ck/NM/Zh/02 belongs to the Dk/HK/Y439/97-like lineage and has a close relationship with that of the Ck/Kor/323/96-like viruses. Therefore, although most of the H9N2 influenza viruses circulating on chicken farms in mainland China belong to the DK/HK/Y280/97-like lineage, the present results indicate that the other two of the three H9N2 lineage viruses also circulate in the chicken population in mainland China.     

Possible mechanisms of the concentration-dependent action of substance P to induce histamine release from rat peritoneal mast cells and the effect of extracellular calcium on mast-cell activation

Rat peritoneal mast cells purified on a Percoll gradient were loaded with the fluorescent Ca²⁺ indicator fura-2 and were challenged with different concentrations of substance P (SP), and intracellular calcium concentrations ([Ca²⁺]_i) were measured by a spectrofluorometric assay. SP at 5 × 10⁻⁶ mol/1 and 10⁻⁵ mol/1 caused a significant histamine release with a significant increase in [Ca²⁺]_i in a dose-dependent manner. However, SP at 10⁻⁸-10⁻⁶ mol/1 did not induce either histamine release or increase in [Ca²⁺]_i. Extracellular calcium at 0.9 mM inhibited the histamine release with a significant reduction of [Ca²⁺]ⁱ compared with that of the cells in a nominally calcium-free condition. These results indicate that the action of SP on rat mast cells relies upon [Ca²⁺]_i to induce histamine release.     

新生期卡介苗和乙肝疫苗联合接种对哮喘小鼠IFN-γ、IL-4和IL-17A表达的影响

目的:观察新生期卡介苗(BCG)和乙肝疫苗(HepB)联合接种对哮喘小鼠干扰素γ(IFN-γ)、白细胞介素4(IL-4)和白细胞介素17A(IL-17A)表达的影响,探讨BCG和HepB联合接种对气道炎症的影响及可能机制。方法:BALB/c小鼠随机分为BCG和HepB联合接种造模[卵清蛋白(OVA)所致哮喘模型]组(B/H/O组)、BCG接种造模组(B/O组)、HepB接种造模组(H/O组)、BCG和HepB联合接种组(B/H组)、造模组(OVA组)、BCG组、HepB组和生理盐水对照(NS)组,每组6只。B/H/O组和B/H组于第0、7和14天分3次皮下注射1×105CFU的BCG,同时第0和28天分2次下肢腿部肌肉注射HepB 1.5μg,其它组单独接种BCG或HepB。OVA致敏和雾化吸入激发建立哮喘模型;末次激发24 h后取肺组织HE染色;收集支气管肺泡灌洗液(BALF)进行细胞总数计数和嗜酸性粒细胞(EOS)计数;ELISA法检测血清IFN-γ和IL-4及肺组织匀浆IL-17A的水平。结果:肺组织病理观察发现,OVA组、B/O组、B/H/O组和H/O组支气管周围大量炎症细胞浸润,气道上皮细胞增生肥大,B/H/O组和H/O组的炎症程度较OVA组重,B/O组则较OVA组轻。B/H/O组、B/O组和H/O组BALF细胞总数与OVA组比较均下降(P0.05);EOS计数在B/H/O组比B/H组上升(P0.05),B/O组比BCG组上升(P0.05),H/O组比HepB组上升(P0.05)。分别与H/O组、OVA组和NS组比较,HepB组的血清IFN-γ/IL-4比值均升高(P0.05);分别与B/H/O组、B/O组、OVA组和NS组比较,B/H组的血清IFN-γ/IL-4比值均升高(P0.05)。与OVA组比较,B/H/O组和B/O组的肺组织匀浆IL-17A水平均下降(P0.05);与B/O组比较,B/H/O组的肺组织匀浆IL-17A水平进一步下降(P0.05)。结论:卡介苗和乙肝疫苗联合接种有助于减轻哮喘模型小鼠肺部的炎症反应,其机制可能与降低IL-4分泌、提高IFN-γ/IL-4水平和抑制IL-17A的表达有关。     

Structurally delineating stromal interaction molecules as the endoplasmic reticulum calcium sensors and regulators of calcium release-activated calcium entry

Summary:  The endoplasmic reticulum (ER) lumen stores a crucial source of calcium (Ca²⁺) maintained orders of magnitude higher than the cytosol for the activation of a plethora of cellular responses transmitted in health and disease by a mutually efficient and communicative exchange of Ca²⁺ between compartments. A coordination of the Ca²⁺ signal is evident in the development of Ca²⁺ release-activated Ca²⁺ (CRAC) entry, vital to lymphocyte activation and replenishing of the ER Ca²⁺ stores, where modest decreases in ER luminal Ca²⁺ induce sustained increases in cytosolic Ca²⁺ sourced from steadfast extracellular Ca²⁺ supplies. While protein sensors that transduce Ca²⁺ signals in the cytosol such as calmodulin are succinctly understood, comparative data on the ER luminal Ca²⁺ sensors is only recently coming to light with the discovery that stromal interaction molecules (STIMs) sense variations in ER stored Ca²⁺ levels in the functional regulation of plasma membrane Orai proteins, the major component of CRAC channel pores. Drawing from data on the role of STIMs in the modulation of CRAC entry, this review illustrates the structural features that delimit the functional characteristics of ER Ca²⁺ sensors relative to well known cytoplasmic Ca²⁺ sensors.