• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Platelet-neutrophil adhesion and neutrophil activation induced by platelet activation.
【24h】

Platelet-neutrophil adhesion and neutrophil activation induced by platelet activation.

机译：血小板活化引起的血小板-中性粒细胞粘附和中性粒细胞活化。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Diverse clinical and animal studies suggest complicated platelet-leukocyte interactions involved in cardiovascular diseases. Augmented platelet-neutrophil adhesion has been observed in thrombotic and inflammatory conditions. Activated platelets modulate neutrophil functions through released proteins, such as P-selectin and platelet factor 4 (PF4). We investigated platelet-neutrophil adhesion and neutrophil activation induced by platelet activation, with focus on the roles of P-selectin and PF4.; In chapter 2, we examined heterotypic interactions between resting neutrophils and either thrombin receptor activating peptide (TRAP) stimulated platelets or P-selectin bearing beads (Ps-beads) under shear from 14-3000/s in cone-plate viscometer and rheometer. Our study reveals an integrin-independent regime for cell adhesion that may be physiologically relevant. While blocking antibodies against either P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1) alone inhibited platelet-neutrophil adhesion by ∼60% at 140/s, these reagents completely blocked adhesion at 3000/s. Anti-Mac-1 alone did not alter platelet-neutrophil adhesion rates, though in synergy with selectin antagonists it abrogated cell binding at all shear rates. Unstimulated neutrophils avidly bound Ps-beads and activated platelets in an integrin-independent manner, suggesting that purely selectin-dependent binding is possible. In support of this, antagonists against P-selectin or PSGL-1 dissociated previously formed platelet-neutrophil and Ps-bead neutrophil aggregates under shear in a variety of experimental systems. In studies where medium viscosity was varied, a subtle shear threshold for P-selectin PSGL-1 binding was also noted at shear rates below 110/s.; In chapter 3, neutrophil activation modulated by PF4 was investigated. We show a mechanism of neutrophil activation induced by PF4 immune complexes. Costimulation of PF4 and anti-PF4 mAb, but not either stimulus alone, induced neutrophil activation marked by Mac-1 upregulation and exocytosis of secondary and tertiary granules. Inhibition studies suggested PF4 mAb recognized neutrophil surface bound PF4 and activated neutrophils through Fc portions of mAb. The process is inhibited by anti-CD32 mAb (IV.3) completely. Similar neutrophil activation was observed when recombinant PF4 (rPF4) was used. PF4 dosage studies showed an optimized PF4 concentration. Introduction of PF4 mutation revealed PF4 activation domains: Pronine-Threonine-Alanine 37-39, Arginine49 and Leucine55. N-terminal mutation was not important for neutrophil activation. Upregulated Mac-1 was shown to mediate neutrophil homotypic aggregation under shear condition.
机译：多样化的临床和动物研究表明，复杂的血小板-白细胞相互作用涉及心血管疾病。在血栓形成和炎性疾病中，血小板-嗜中性粒细胞的粘附增强。活化的血小板通过释放的蛋白质（例如P-选择蛋白和血小板因子4（PF4））调节嗜中性粒细胞的功能。我们研究了血小板活化引起的血小板-中性粒细胞粘附和中性粒细胞活化，重点是P-选择蛋白和PF4的作用。在第2章中，我们研究了静息中性粒细胞与凝血酶受体激活肽（TRAP）刺激的血小板或带有P-选择素的珠子（Ps-beads）在锥板粘度计和流变仪中以14-3000 / s的剪切力之间的异型相互作用。我们的研究表明细胞粘附的整合素独立方案可能是生理相关的。虽然仅阻断针对P-选择蛋白或P-选择蛋白糖蛋白配体1（PSGL-1）的抗体在140 / s时抑制血小板-中性粒细胞粘附约60％，但这些试剂在3000 / s时完全阻断了粘附。单独使用抗Mac-1并不会改变血小板中性粒细胞的黏附率，尽管与选择素拮抗剂协同作用会消除所有剪切速率下的细胞结合。未刺激的嗜中性粒细胞以整联蛋白独立的方式狂热地结合Ps珠和活化的血小板，这表明纯选择素依赖性结合是可能的。为此，在各种实验系统中，P-选择蛋白或PSGL-1拮抗剂在剪切作用下解离了先前形成的血小板中性粒细胞和Ps珠粒中性粒细胞聚集体。在中等粘度变化的研究中，在剪切速率低于110 / s时，P-选择素PSGL-1结合的剪切阈值也很微弱。在第三章中，研究了PF4调节的中性粒细胞活化。我们显示了由PF4免疫复合物诱导的中性粒细胞激活机制。 PF4和抗PF4 mAb的共刺激，但不是单独刺激，都以Mac-1上调以及次级和第三级颗粒的胞吐作用为特征，诱导中性粒细胞活化。抑制研究表明，PF4 mAb可识别中性粒细胞表面结合的PF4，并通过mAb的Fc部分激活中性粒细胞。该过程完全被抗CD32 mAb（IV.3）抑制。当使用重组PF4（rPF4）时，观察到类似的嗜中性粒细胞活化。 PF4剂量研究显示了最佳的PF4浓度。 PF4突变的引入揭示了PF4激活域：脯氨酸-苏氨酸-丙氨酸37-39，精氨酸49和亮氨酸55。 N端突变对于中性粒细胞活化并不重要。上调的Mac-1被证明在剪切条件下介导嗜中性粒细胞同型聚集。

著录项

  • 作者

    Xiao, Zhihua.;

  • 作者单位

    State University of New York at Buffalo.$bChemical and Biological Engineering.;

  • 授予单位 State University of New York at Buffalo.$bChemical and Biological Engineering.;
  • 学科 Engineering Biomedical.; Engineering Chemical.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 167 p.
  • 总页数 167
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物医学工程;化工过程（物理过程及物理化学过程）;
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号