血小板在双边的IL-33驱动的前循环中与巨细胞进行接触
Airi Nishida1, Jun Nagai1,2,3, Madeline Hastings1
1Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, MA 02115.
概括
血小板和乳腺细胞形成一个前循环,放大2型炎症,特别是在喘等疾病中. 这种由IL-33驱动的相互作用涉及血小板激活和媒介释放,突出显示了一种新的先天免疫路径.
科学领域:
- 免疫学 免疫学 免疫学
- 呼吸系统医学 呼吸系统医学
- 细胞生物学 细胞生物学
背景情况:
- 已知血小板通过不完全理解的机制放大2型炎症 (T2I).
- 在阿司匹林加剧呼吸道疾病 (AERD) 模型中,乳腺细胞 (MC) 激活取决于IL-33和cysteinyl leukotrienes (cysLTs),并因血小板枯竭而减弱.
研究的目的:
- 阐明血小板放大T2I的机制,重点关注血小板和乳腺细胞之间的相互作用.
- 研究IL-33在潜在的前循环中的作用,其中包括血小板和乳腺细胞在呼吸道炎症中的作用.
主要方法:
- 利用AERD的小鼠模型,涉及阿司匹林挑战和支气管支气管洗液 (BAL) 分析.
- 刺激的小鼠骨髓衍生性巨细胞 (BMMCs) 具有IL-33和评估的血小板激活标志物 (CXCL7,CD62P) 和媒介体生产 (PGD2,LTC4).
- 采用杆细胞特异性LTC4和血小板特异性CysLT2R的遗传删除,并研究了P2Y1受体的作用.
主要成果:
- 从AERD样小鼠的BAL液中,IL-33中和降低了cysLTs和CXCL7.
- 在严重喘患者中,BAL液体的PGD2水平与CXCL7和MC三酶相关.
- 血小板通过IL-33刺激的BMMC增强了PGD2和LTC4的产生,从而导致血小板激活.
- 遗传删除MC-LTC4或血小板-CysLT2R废除的血小板激活和媒介放大.
- 血小板衍生的ADP/ATP和MC P2Y1受体对于这种相互作用至关重要.
结论:
- 确定了血小板和巨细胞之间的IL-33驱动的前循环,可以放大T2I.
- 这种依赖于cysLTs和P2Y1受体的MC-血小板交叉作用,有助于喘中的IL-33介导免疫病理.
- 这一途径代表了T2I驱动的呼吸系统疾病的潜在治疗标.
相关概念视频
Formation of the Platelet Plug
8.5K
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...
8.5K
Structure and Function of Platelets
2.8K
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 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...
2.8K
Inflammation
61.4K
Overview
61.4K
Intracellular Signaling Affects Focal Adhesions
3.4K
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...
3.4K
Differentiation of Common Myeloid Progenitor Cells
3.9K
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
3.9K
IP3/DAG Signaling Pathway
14.1K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
14.1K


