补体和血小板:原血栓细胞激活需要膜攻击复杂诱导的释放危险信号
Marco Mannes1, Veronika Pechtl2, Susanne Hafner2
1Institute of Clinical and Experimental Trauma Immunology, University Hospital of Ulm, Ulm, Germany.
Blood advances
|July 10, 2023
概括
补充激活导致PNH和aHUS中的血栓. 阻断终端补充通路通过阻止细胞溶解和ADP释放来防止血栓,这解释了为什么抗补充疗法是有效的.
科学领域:
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
- 病理生理学 病理生理学
背景情况:
- 补充激活驱动在阳性夜间血红蛋白尿症 (PNH) 和非典型血清性尿素综合征 (aHUS) 中的血栓形成.
- 目前的抗补剂疗法可以预防血栓事件,但确切的机制尚不清楚.
- 抗凝血和抗血小板疗法在很大程度上对补体驱动的血栓形成无效.
研究的目的:
- 阐明补充激活导致PNH和aHUS中血栓事件的机制.
- 研究补充成分和途径在血小板激活和血栓形成中的作用.
- 为了确定为什么抗补充疗法在预防这些疾病中的血栓形成方面是有效的.
主要方法:
- 使用全人血液进行体外研究,以评估补充介导的血小板激活.
- 功能性测定测量血小板对补充性毒素 (C3a,C5a) 和补充激活产品的反应.
- 在体内验证使用不匹配的红细胞输血,补充抑制 (OmCI) 和蛇毒因子的老鼠模型.
主要成果:
- 在全血中补充介导的血液溶解诱导了血小板激活,类似于腺5'-二酸盐 (ADP).
- 阻断补充成分C3或C5取消了血小板激活.
- 血小板对性毒素C3a和C5a没有反应;仅在膜攻击复合体 (MAC) 介导的细胞解时才发生前血栓激活.
- ADP受体对抗剂甚至在完全补充激活期间也抑制了血小板激活.
- 在体内研究证实,只有当MAC介导细胞解发生时,血栓形成才会发生.
结论:
- 补充激活仅在终端途径以MAC介导的细胞内ADP释放为高潮时才能诱导实质性的前血栓细胞激活.
- 这种机制解释了抗补充疗法在预防血栓栓塞的有效性,而不会影响正常的血液静止.
更多相关视频
05:49Procoagulant Platelet Characterization by Measuring Phosphatidylserine Exposure and Microvesicle Release from Human Purified Platelets
Published on: November 29, 2024
629
08:50Laminar Flow-based Assays to Investigate Leukocyte Recruitment on Cultured Vascular Cells and Adherent Platelets
Published on: April 9, 2018
7.6K
相关概念视频
Complement System
2.4K
The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
2.4K
Extrinsic and Intrinsic Pathways of Hemostasis
8.4K
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
8.4K
Formation of the Platelet Plug
6.7K
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...
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...
6.7K
The Extrinsic Apoptotic Pathway
6.5K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.5K
Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K
Inflammation
53.9K
Overview
53.9K
