α6 integrins participate in pro-T cell homing to the thymus

During embryogenesis, colonization of the thymic rudiment by hemopoietic progenitor cells depends on the adhesion of these cells to the jugular endothelium. Previously, we showed that progenitor T cells (pro-T cells) interact with α₆ integrins present on vascular endothelium. Here, we demonstrate that anti-α₆ integrin antibodies reduced the number of thymocytes up to 80 % in a congenic mouse model for thymus colonization by pro-T cells. In organotypic thymus cultures, the anti-α₆ integrin antibodies did not influence T cell development and proliferation. From this, we conclude that α₆ integrin participates in thymus homing. During mouse thymus ontogeny, α₆ integrin mRNA and protein expression was found as early as day 10 of development; at day 11, perithymic endothelial cells were α₆ integrin positive. Two α₆ integrin mRNA exist which are produced by alternative exon usage. The longer form, α₆, integrin, predominates during early embryonic stages, while the shorter α_6A form was present later during development. Although α₆, integrins can be displayed by immature thymocytes, strongest expression was found on intra- and perithymic vascular endothelium. These data suggest that α₆ integrins are involved in the homing of pro-T cells to the developing thymus by mediating adhesion of pro-T cells to the vascular endothelium.     

Control of fluid shear response in circulating leukocytes by integrins

Recent evidence shows that circulating leukocytes respond not only to humoral inflammatory mediators but also to fluid stresses. Application of fluid shear stress (of the order of 1–10 cm² to fresh migrating leukocytes leads to initial retraction of pseudopods, an important step to facilitate normal passage of leukocytes through the microcirculation and to prevent spreading on the endothelium. The ability to respond to fluid shear stress, however, may be regulated under different physiological conditions. In the current study, we examine the role of integrins in the fluid shear response as measured by pseudopod retraction with the use of antibodies against human neutrophil ₁ and ₂ integrins. Neutrophils adhering via ₂ integrins exhibit normal ability to project pseudopods and to migrate. Such cells show normal response to fluid shear with rapid pseudopod retraction. In contrast, attachment via ₁ integrins leads to firmly adhesive leukocytes, spreading and almost no cell migration. Such leukocytes exhibit a significantly attenuated ability for pseudopod retraction under fluid shear. These results suggest that integrins may serve as a regulating mechanism for fluid shear response in human leukocytes. Attachment via ₁ integrins may lead to an abolishment of the fluid shear response. © 2002 Biomedical Engineering Society. PAC2002: 8716-b, 8719Tt     

Differential expression of matrilysin-1 (MMP-7), 92 kD gelatinase (MMP-9), and metalloelastase (MMP-12) in oral verrucous and squamous cell cancer

Squamous cell carcinoma (SCC) of the oral cavity is a highly invasive tumour of stratified squamous epithelium that spreads through degradation of the basement membrane (BM) and extracellular matrix (ECM). There are currently no reliable tissue or serum markers to predict whether the tumour has metastasized at the time of diagnosis. Verrucous carcinoma (VC) of the oral cavity is a rare low-grade variant of oral SCC that penetrates into the subepithelial connective tissue. Many matrix metalloproteinases (MMPs), such as MMP-1, -2, -7, -9, -13, and -14, as well as integrin receptors have been implicated in cancer invasion. Integrin alphavbeta6 is induced in SCC and appears to be involved in up-regulation of MMP-9 expression by oral keratinocytes and promotion of their migration. The aim of this study was to investigate whether the pattern of MMP expression or that of alphavbeta6 integrin contributes to the differences in the biological behaviour of oral SCC and VC. The results show that the less aggressive nature of oral VC may be connected to its MMP expression profile. Typically, VCs were devoid of epithelial MMP-3, -7, -9, -12 and -13 expression, compared with SCCs. MMP-19 was expressed by epithelial keratinocytes in hyperproliferative areas of verrucous hyperplasia, VC, and SCC, but was absent in the invasive cancer cell nests of SCC. MMP-26 was expressed by hyperproliferative keratinocytes in VC as well as by invasive cancer cells in SCCs. MMP-10 was expressed widely in the epithelium of all SCC specimens. alphavbeta6 integrin expression was also detected in some cases of epithelial hyperplasia but was significantly more abundant in cancers at the invasive front. The absence of MMP-7, -9 and -12 from epithelial cells may serve as a good prognostic marker of non-invasive oral carcinoma. Blocking the activity of invasion-specific MMPs or alphavbeta6 integrin might offer novel therapeutic modalities in early-stage oral carcinoma.     

ITGβ1、IFI16、TTR血清水平与妊娠期高血压疾病进展程度关联性及临床表达意义探究

目的 探究整合素β1(integrin β1,ITGβ1)、人γ干扰素诱导蛋白16(interferon - inducible protein 16,IFI16)、转甲状腺素蛋白(transthyretin,TTR)血清水平与妊娠期高血压疾病进展程度关联性及临床表达意义。 方法 选取2018年11月—2020年1月在攀枝花市中心医院住院分娩的妊娠期高血压疾病患者91例为研究组,另随机选取同期正常妊娠孕妇91例为对照组。对比两组血清ITGβ1、IFI16、TTR水平,采用Spearson秩相关分析血清各指标与妊娠期高血压疾病进展程度的相关性,采用受试者工作(receiver operating characteristic,ROC)曲线分析探讨血清各指标对妊娠期高血压疾病患者妊娠结局的预测价值。 结果 研究组血清ITGβ1、IFI16水平高于对照组,血清TTR水平低于对照组(P＜0.05);妊娠期高血压疾病进展程度与血清ITGβ1、IFI16水平呈正相关,与血清TTR水平呈负相关(P＜0.05);血清ITGβ1＞2.38 ng/ml、IFI16＞24.39 ng/ml、TTR≤315.08 mg/L联合预测妊娠期高血压疾病患者有无不良妊娠结局的曲线下面积(area under the carve,AUC)为0.861,大于各指标单一预测的AUC(0.782、0.813、0.790),联合预测的敏感度、特异度分别为80.00%、81.82%。 结论 妊娠期高血压疾病患者血清ITGβ1、IFI16表达明显升高,血清TTR表达水平降低,与妊娠期高血压疾病的发生及病情进展程度密切相关,且能辅助临床预测患者妊娠结局。     

β1整合素基因缺失对Gi蛋白分布的影响

目的 了解跨膜蛋白β1整合素对信号分子G蛋白细胞内构型的影响,为进一步研究β1整合素在信号传导中的作用打下基础。方法 采用荧光双标记及重叠合显微镜分析技术,观察野生型胚胎干细胞系（D3细胞）,β1整合素基因敲除胚胎干细胞（G201细胞）,β1整合素基因敲除后再植入胚胎干细胞（G201N）及小鼠胚胎心肌细胞中多种G蛋白（Gas,Gai1-3,Gao,Gai/o/t/z）细胞内构型特点和差异。结果 Gas,Gao,Gai/o/t/z在上述几种细胞系中均呈弥温性分布,未能发现明显差异,与此不同的是Gai1-3在D3细胞源性心肌细胞内呈网状分布,在非心肌细胞内呈线条状分布,而在G201细胞中Gi上述特异性构型被打乱,呈近似于弥漫样分布,值得注意的是在β1整合素重新恢复的G201N细胞Gi构型又呈网样或线条样分布,与野生型胚胎干细胞中Gi的构型相一致。结论 β1整合素能够影响信号分子Gi蛋白的细胞内定位,推测β1整合素可通过改变Gi的分布而影响Gi介导的信号传导。     

过表达整合蛋白α5β1的SMMC7721细胞株的建立和鉴定

构建过表达整合蛋白α５β１的ＳＭＭＣ７７２１细胞株。方法应用分子克隆技术和基因转染建立过表达整合蛋白α５β１的ＳＭＭＣ７７２１细胞株,应用ＲＴ－ＰＣＲ及流式细胞术鉴定ＳＭＭＣ７７２１细胞表面整合蛋白α５β１的表达。结果获得过表达整合蛋白α５／β１的ＳＭＭＣ７７２１细胞株α５．３－７７２１,β１．６－７７２１,α５β１．６－７７２１细胞。结论整合蛋白α５β１基因转染后,ＳＭＭＣ７７２１细胞整合蛋白α５β１的ＲＮＡ及蛋白质表达明显提高。过表达整合蛋白α５β１的ＳＭＭＣ７７２１细胞株的建立有助于研究整合蛋白α５β１在肝癌中的作用     

Structure,function and biological properties of integrin αvβ3on human melanoma cells

Summary Human melanoma represents one of the most metastatic cancers in man. The capacity of melanoma cells to invade a variety of tissues and extracellular matrices is, in part, due to their repertoire of adhesion receptors. To this end, human melanoma cells express multiple integrin cell adhesion receptors among these is the vitronectin receptor, _v3. This adhesion receptor enables melanoma cells to attach to a wide variety of extracellular matrix components containing the sequence Arg-Gly-Asp. This review will focus on the biosynthetic, biochemical and biological properties of this receptor expressed on the surface of human melanoma cells.     

整合素与肿瘤转移

整合素是一类介导细胞与细胞外基质及细胞与细胞间黏附的细胞黏附分子受体.肿瘤细胞的生长、分化、浸润及转移等行为与细胞黏附密切相关.全文就整合素与肿瘤转移关系作一综述.     

整合素与肿瘤血管生成

整合素家族是一类黏附分子,表达于内皮细胞,在肿瘤的血管生成过程中起着极为重要的作用.许多细胞因子促进肿瘤的血管生成是通过整合素的介导作用实现的,先引起整合素表达的变化,进一步引起内皮细胞的增殖、迁移.     

那他珠单抗治疗多发性硬化研究进展

α4β1整合素在多发性硬化发病机制的最早环节中起关键作用,阻断α4整合素可防止自身免疫细胞通过与中枢神经的微血管粘附而进入中枢神经系统,从而减轻炎症性脱髓鞘反应。那他珠单抗是针对整合素的α4亚单位的单克隆抗体,临床试验表明主要通过抑制粘附过程而防止出现新病灶,对已有病灶也有减轻炎症反应的作用,从而减少复发。