共查询到20条相似文献，搜索用时 453 毫秒
1.
Yoder J Pham C Iizuka YM Kanagawa O Liu SK McGlade J Cheng AM 《Science (New York, N.Y.)》2001,291(5510):1987-1991
GADS is an adaptor protein implicated in CD3 signaling because of its ability to link SLP-76 to LAT. A GADS-deficient mouse was generated by gene targeting, and the function of GADS in T cell development and activation was examined. GADS- CD4-CD8- thymocytes exhibited a severe block in proliferation but still differentiated into mature T cells. GADS- thymocytes failed to respond to CD3 cross-linking in vivo and were impaired in positive and negative selection. Immunoprecipitation experiments revealed that the association between SLP-76 and LAT was uncoupled in GADS- thymocytes. These observations indicate that GADS is a critical adaptor for CD3 signaling. 相似文献
2.
Peterson EJ Woods ML Dmowski SA Derimanov G Jordan MS Wu JN Myung PS Liu QH Pribila JT Freedman BD Shimizu Y Koretzky GA 《Science (New York, N.Y.)》2001,293(5538):2263-2265
SLAP-130/Fyb (SLP-76-associated phosphoprotein or Fyn-binding protein; also known as Fyb/Slap) is a hematopoietic-specific adapter, which associates with and modulates function of SH2-containing leukocyte phosphoprotein of 76 kilodaltons (SLP-76). T cells from mice lacking SLAP-130/Fyb show markedly impaired proliferation following CD3 engagement. In addition, the T cell receptor (TCR) in SLAP-130/Fyb mutant cells fails to enhance integrin-dependent adhesion. Although TCR-induced actin polymerization is normal, TCR-stimulated clustering of the integrin LFA-1 is defective in SLAP-130/Fyb-deficient cells. These data indicate that SLAP-130/Fyb is important for coupling TCR-mediated actin cytoskeletal rearrangement with activation of integrin function, and for T cells to respond fully to activating signals. 相似文献
3.
Hood JD Bednarski M Frausto R Guccione S Reisfeld RA Xiang R Cheresh DA 《Science (New York, N.Y.)》2002,296(5577):2404-2407
Efforts to influence the biology of blood vessels by gene delivery have been hampered by a lack of targeting vectors specific for endothelial cells in diseased tissues. Here we show that a cationic nanoparticle (NP) coupled to an integrin alphavbeta3-targeting ligand can deliver genes selectively to angiogenic blood vessels in tumor-bearing mice. The therapeutic efficacy of this approach was tested by generating NPs conjugated to a mutant Raf gene, ATPmu-Raf, which blocks endothelial signaling and angiogenesis in response to multiple growth factors. Systemic injection of the NP into mice resulted in apoptosis of the tumor-associated endothelium, ultimately leading to tumor cell apoptosis and sustained regression of established primary and metastatic tumors. 相似文献
4.
Gu Y Filippi MD Cancelas JA Siefring JE Williams EP Jasti AC Harris CE Lee AW Prabhakar R Atkinson SJ Kwiatkowski DJ Williams DA 《Science (New York, N.Y.)》2003,302(5644):445-449
The Rho guanosine triphosphatases (GTPases) Rac1 and Rac2 are critical signaling regulators in mammalian cells. The deletion of both Rac1 and Rac2 murine alleles leads to a massive egress of hematopoietic stem/progenitor cells (HSC/Ps) into the blood from the marrow, whereas Rac1-/- but not Rac2-/- HSC/Ps fail to engraft in the bone marrow of irradiated recipient mice. In contrast, Rac2, but not Rac1, regulates superoxide production and directed migration in neutrophils, and in each cell type, the two GTPases play distinct roles in actin organization, cell survival, and proliferation. Thus, Rac1 and Rac2 regulate unique aspects of hematopoietic development and function. 相似文献
5.
Thurston G Suri C Smith K McClain J Sato TN Yancopoulos GD McDonald DM 《Science (New York, N.Y.)》1999,286(5449):2511-2514
Angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF) are endothelial cell-specific growth factors. Direct comparison of transgenic mice overexpressing these factors in the skin revealed that the VEGF-induced blood vessels were leaky, whereas those induced by Ang1 were nonleaky. Moreover, vessels in Ang1-overexpressing mice were resistant to leaks caused by inflammatory agents. Coexpression of Ang1 and VEGF had an additive effect on angiogenesis but resulted in leakage-resistant vessels typical of Ang1. Ang1 therefore may be useful for reducing microvascular leakage in diseases in which the leakage results from chronic inflammation or elevated VEGF and, in combination with VEGF, for promoting growth of nonleaky vessels. 相似文献
6.
Receptor-mediated transport of insulin across endothelial cells 总被引：33，自引：0，他引：33
Hormones such as insulin are transported from the interior to the exterior of blood vessels. Whether endothelial cells, which line the inner walls of blood vessels have a role in this transport of hormones is not clear, but it is known that endothelial cells can internalize and release insulin rapidly with little degradation. The transport of iodine-125-labeled insulin was measured directly through the use of dual chambers separated by a horizontal monolayer of cultured bovine aortic endothelial cells. In this setting, endothelial cells took up and released the labeled insulin, thereby transporting it across the cells. The transport of insulin across the endothelial cells was temperature sensitive and was inhibited by unlabeled insulin and by antibody to insulin receptor in proportion to the ability of these substances to inhibit insulin binding to its receptor. More than 80 percent of the transported insulin was intact. These data suggest that insulin is rapidly transported across endothelial cells by a receptor-mediated process. 相似文献
7.
Gu C Yoshida Y Livet J Reimert DV Mann F Merte J Henderson CE Jessell TM Kolodkin AL Ginty DD 《Science (New York, N.Y.)》2005,307(5707):265-268
The development of a patterned vasculature is essential for normal organogenesis. We found that signaling by semaphorin 3E (Sema3E) and its receptor plexin-D1 controls endothelial cell positioning and the patterning of the developing vasculature in the mouse. Sema3E is highly expressed in developing somites, where it acts as a repulsive cue for plexin-D1-expressing endothelial cells of adjacent intersomitic vessels. Sema3E-plexin-D1 signaling did not require neuropilins, which were previously presumed to be obligate Sema3 coreceptors. Moreover, genetic ablation of Sema3E or plexin-D1 but not neuropilin-mediated Sema3 signaling disrupted vascular patterning. These findings reveal an unexpected semaphorin signaling pathway and define a mechanism for controlling vascular patterning. 相似文献
8.
The embryonic role of endothelial cells and nascent vessels in promoting organogenesis, prior to vascular function, is unclear. We find that early endothelial cells in mouse embryos surround newly specified hepatic endoderm and delimit the mesenchymal domain into which the liver bud grows. In flk-1 mutant embryos, which lack endothelial cells, hepatic specification occurs, but liver morphogenesis fails prior to mesenchyme invasion. We developed an embryo tissue explant system that permits liver bud vasculogenesis and show that in the absence of endothelial cells, or when the latter are inhibited, there is a selective defect in hepatic outgrowth. We conclude that vasculogenic endothelial cells and nascent vessels are critical for the earliest stages of organogenesis, prior to blood vessel function. 相似文献
9.
Modulation of the sis gene transcript during endothelial cell differentiation in vitro 总被引：26，自引：0，他引：26
M Jaye E McConathy W Drohan B Tong T Deuel T Maciag 《Science (New York, N.Y.)》1985,228(4701):882-885
10.
为研究苜蓿皂苷(Alfalfa saponin)对X射线照射小鼠造血系统的影响,选取雄性SPF级昆明系小鼠90只,随机分为对照组和试验组,研究25、50和100mg/ml的苜蓿皂苷对X射线照射强度为4.0Gy小鼠造血系统的影响和不同剂量X射线对添加25mg/ml的小鼠造血系统的影响。结果表明:1)预防性给予25mg/mL苜蓿皂苷,可显著减轻4.0Gy的X射线对小鼠外周血白细胞(White blood cells,WBC)、红细胞(Red blood cells,RBC)和血小板(Platelets,PLT)数量的降低程度(P0.05),增加照射小鼠的骨髓有核细胞(Bone marrow nucleated cells,BMC)数(P0.05),显著降低微核率(P0.05)。2)预防性给予25mg/mL的苜蓿皂苷,相同照射剂量的试验组小鼠白细胞、红细胞、血小板和骨髓有核细胞数显著高于对照组(P0.05),微核率显著低于对照组(P0.05)。3)随照射强度增加,25mg/ml的苜蓿皂苷保护小鼠受辐射损伤的能力下降。综上,苜蓿皂苷可缓解X射线对小鼠造血系统和染色体的损伤,苜蓿皂苷浓度与射线强度存在量效关系,需要根据不同的照射强度添加不同浓度的苜蓿皂苷。 相似文献
11.
Shaked Y Ciarrocchi A Franco M Lee CR Man S Cheung AM Hicklin DJ Chaplin D Foster FS Benezra R Kerbel RS 《Science (New York, N.Y.)》2006,313(5794):1785-1787
The contribution of bone marrow-derived circulating endothelial progenitor cells (CEPs) to tumor angiogenesis has been controversial, primarily because of their low numbers in blood vessels of untreated tumors. We show that treatment of tumor-bearing mice with vascular disrupting agents (VDAs) leads to an acute mobilization of CEPs, which home to the viable tumor rim that characteristically remains after such therapy. Disruption of this CEP spike by antiangiogenic drugs or by genetic manipulation resulted in marked reductions in tumor rim size and blood flow as well as enhanced VDA antitumor activity. These findings also provide a mechanistic rationale for the enhanced efficacy of VDAs when combined with antiangiogenic drugs. 相似文献
12.
为研究胚胎不同时期VEGF、KDR和CD34在人卵黄囊中的表达情况,了解胚胎造血的发育过程和机理。采用免疫组织化学SP法卵黄囊冰冻切片进行染色,光镜观察。结果发现在第3￣4周的人卵黄囊低表达VEGF和KDR,不表达CD34。4￣6周组强表达VEGF、KDR和CD34。在血岛内阳性细胞大而圆,成簇或分散聚集,有些细胞沿血岛边缘形成血管样结构。6周以后,卵黄囊弱表达VEGF、KDR和CD34。上述结果提示卵黄囊可表达造血和血管生成相关因子,随胚胎发育呈阶段性表达。卵黄囊中出现造血干细胞和血管内皮细胞的分化。 相似文献
13.
Purification and characterization of mouse hematopoietic stem cells 总被引：181，自引：0，他引：181
Mouse bone marrow hematopoietic stem cells were isolated with the use of a variety of phenotypic markers. These cells can proliferate and differentiate with approximately unit efficiency into myelomonocytic cells, B cells, or T cells. Thirty of these cells are sufficient to save 50 percent of lethally irradiated mice, and to reconstitute all blood cell types in the survivors. 相似文献
14.
Burdelya LG Krivokrysenko VI Tallant TC Strom E Gleiberman AS Gupta D Kurnasov OV Fort FL Osterman AL Didonato JA Feinstein E Gudkov AV 《Science (New York, N.Y.)》2008,320(5873):226-230
The toxicity of ionizing radiation is associated with massive apoptosis in radiosensitive organs. Here, we investigate whether a drug that activates a signaling mechanism used by tumor cells to suppress apoptosis can protect healthy cells from the harmful effects of radiation. We studied CBLB502, a polypeptide drug derived from Salmonella flagellin that binds to Toll-like receptor 5 (TLR5) and activates nuclear factor-kappaB signaling. A single injection of CBLB502 before lethal total-body irradiation protected mice from both gastrointestinal and hematopoietic acute radiation syndromes and resulted in improved survival. CBLB502 injected after irradiation also enhanced survival, but at lower radiation doses. It is noteworthy that the drug did not decrease tumor radiosensitivity in mouse models. CBLB502 also showed radioprotective activity in lethally irradiated rhesus monkeys. Thus, TLR5 agonists could potentially improve the therapeutic index of cancer radiotherapy and serve as biological protectants in radiation emergencies. 相似文献
15.
水通道蛋白在小鼠嗅上皮中的免疫定位 总被引：1，自引：0，他引：1
采用免疫印迹和免疫组织化学技术分析水通道蛋白(Aquaporins,AQPs)在小鼠嗅上皮细胞中的表达情况。结果表明:AQP1在血管内皮细胞表达,AQP3在下层支持细胞和基底细胞表达,AQP4在上层支持细胞和基底细胞表达;AQP5在嗅毛和鲍曼氏腺的分泌细胞和导管细胞表达。结果显示了水通道蛋白在小鼠嗅上皮细胞中的表达位置,其中在支持细胞和基底细胞表达的AQP3和AQP4可能为嗅神经功能的维持提供了重要的微环境,在嗅毛和鲍曼氏腺的分泌细胞和导管细胞表达的AQP5可能在气味的感受方面起作用。 相似文献
16.
Griffin CT Srinivasan Y Zheng YW Huang W Coughlin SR 《Science (New York, N.Y.)》2001,293(5535):1666-1670
The coagulation protease thrombin triggers fibrin formation, platelet activation, and other cellular responses at sites of tissue injury. We report a role for PAR1, a protease-activated G protein-coupled receptor for thrombin, in embryonic development. Approximately half of Par1-/- mouse embryos died at midgestation with bleeding from multiple sites. PAR1 is expressed in endothelial cells, and a PAR1 transgene driven by an endothelial-specific promoter prevented death of Par1-/- embryos. Our results suggest that the coagulation cascade and PAR1 modulate endothelial cell function in developing blood vessels and that thrombin's actions on endothelial cells-rather than on platelets, mesenchymal cells, or fibrinogen-contribute to vascular development and hemostasis in the mouse embryo. 相似文献
17.
18.
Involvement of sialic acid on endothelial cells in organ-specific lymphocyte recirculation 总被引：38，自引：0，他引：38
Mouse lymphocytes incubated on cryostat-cut sections of lymphoid organs (lymph nodes and Peyer's patches) specifically adhere to the endothelium of high endothelial venules (HEV), the specialized blood vessels to which recirculating lymphocytes attach as they migrate from the blood into the parenchyma of the lymphoid organs. Treatment of sections with sialidase eliminated the binding of lymphocytes to peripheral lymph node HEV, had no effect on binding to Peyer's patch HEV, and had an intermediate effect on mesenteric lymph node HEV. These results suggest that sialic acid on endothelial cells may be an organ-specific recognition determinant for lymphocyte attachment. 相似文献
19.
Tissue factor (thromboplastin): localization to plasma membranes by peroxidase-conjugated antibodies 总被引：10，自引：0，他引：10
Peroxidase-conjugated antibodies were used to determine the histologic and cytologic localization of bovine and human tissue factor (thromboplastin). Tissue factor antigen was found in highest concentration in the intima of blood vessels, particularly in the plasma membranes of endothelial cells and in human atheromatous plaques. Tissue factor was also found limited to the plasma membranes of many cell types. The presence of tissue factor in the plasma membranes of endothelial cells and atheromata suggests that it may play a significant role in hemostasis and thrombosis. 相似文献
20.
Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate 总被引：1，自引：0，他引：1
Pappu R Schwab SR Cornelissen I Pereira JP Regard JB Xu Y Camerer E Zheng YW Huang Y Cyster JG Coughlin SR 《Science (New York, N.Y.)》2007,316(5822):295-298
Lymphocytes require sphingosine-1-phosphate (S1P) receptor-1 to exit lymphoid organs, but the source(s) of extracellular S1P and whether S1P directly promotes egress are unknown. By using mice in which the two kinases that generate S1P were conditionally ablated, we find that plasma S1P is mainly hematopoietic in origin, with erythrocytes a major contributor, whereas lymph S1P is from a distinct radiation-resistant source. Lymphocyte egress from thymus and secondary lymphoid organs was markedly reduced in kinase-deficient mice. Restoration of S1P to plasma rescued egress to blood but not lymph, and the rescue required lymphocyte expression of S1P-receptor-1. Thus, separate sources provide S1P to plasma and lymph to help lymphocytes exit the low-S1P environment of lymphoid organs. Disruption of compartmentalized S1P signaling is a plausible mechanism by which S1P-receptor-1 agonists function as immunosuppressives. 相似文献