血小板多酸盐在体内是促炎和促凝的介质
Felicitas Müller1, Nicola J Mutch, Wolfdieter A Schenk
1Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm S-171 76, Sweden.
Cell
|December 17, 2009
概括
活化血小板释放无机聚酸盐 (polyP),这是一种触发炎症和血液凝结的分子. 用酸酶准polyP减少了小鼠的血小板驱动的血栓形成和炎症.
科学领域:
- 生物化学 生物化学
- 血液学 血液学 血液学
- 免疫学 免疫学 免疫学
背景情况:
- 血小板在血液静止,血栓形成和炎症中至关重要.
- 将血小板与这些过程联系在一起的分子机制正在研究中.
研究的目的:
- 研究激活血小板释放的无机聚酸盐 (polyP) 的作用.
- 为了确定多聚的参与血栓形成,炎症和凝血.
主要方法:
- 研究了polyP与XII因子的结合及其激活.
- 评估了polyP对小鼠中的布拉迪基宁释放和血管透性的影响.
- 研究了XII因子,布拉迪基宁受体和酸酶对多聚中介作用的影响.
- 检查了polyP在血凝固和肺栓塞模型中的作用.
- 分析了Hermansky-Pudlak综合征患者血中polyP的影响.
主要成果:
- 激活的血小板释放PolyP,从而激活XII因子并触发布拉迪基宁的释放.
- 聚增加了血管透性和液体外流,其影响取决于XII因子和布拉迪基宁受体.
- PolyP通过接触途径启动血凝固,并导致致命的肺栓塞.
- 用酸酶准polyP抑制了血小板前凝活动和血栓形成.
- 添加PolyP可以在赫曼斯基-普德拉克综合征患者的血中纠正缺陷的凝血.
结论:
- 无机聚酸盐 (polyP) 是激活血小板释放的新型媒介.
- 聚聚在血小板驱动的炎症和前凝性疾病中起着根本性的作用.
- 向polyP对血栓性和炎症性疾病具有潜在的治疗策略.
相关概念视频
01:42Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
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01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
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Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
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01:18Structure and Function of Platelets
The cell fragments known as platelets are disc-shaped, with an average diameter of about 3 μm and a thickness of roughly 1 μm. They play a crucial role in the body's vascular clotting system, which also involves plasma proteins, blood cells, and blood vessel tissues.
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000 platelets, with...
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01:22Formation of the Platelet Plug
The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
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01:16Clot Retraction and Fibrinolysis
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.