Related Experiment Video

Updated: Apr 17, 2026

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages
08:41

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages

Published on: April 6, 2022

3.2K

Caspase-1-mediated pathway promotes generation of thromboinflammatory microparticles

Andrea S Rothmeier, Patrizia Marchese, Brian G Petrich

    The Journal of Clinical Investigation
    |February 24, 2015
    PubMed

    Insights

    Extracellular ATP signals tissue damage, activating macrophages. This triggers a pathway involving inflammasomes and microparticles, promoting both inflammation and thrombosis.

    Area of Science:

    • Immunology
    • Cell Biology
    • Thrombosis

    Background:

    • Extracellular ATP signals tissue damage, activating macrophages.
    • Macrophage responses amplify inflammation and coagulation.
    • P2X7 receptors mediate ATP signaling in macrophages.

    Purpose of the Study:

    • To elucidate the mechanism by which ATP signaling activates macrophages.
    • To investigate the role of the thioredoxin system and inflammasome in this process.
    • To identify pathways linking inflammation and thrombosis.

    Main Methods:

    • Studied ATP signaling via P2X7 receptors in macrophages.
    • Investigated inflammasome activation and reactive oxygen species (ROS) generation.
    • Analyzed thioredoxin (TRX)/TRX reductase (TRXR) system function.
    • Examined filopodia formation, microparticle (MP) generation, and tissue factor (TF) trafficking.

    Main Results:

    • ATP/P2X7 signaling uncoupled TRX/TRXR system and activated inflammasome via ROS.
    • Inflammasome activation promoted procoagulant MP release dependent on the thiol pathway.
    • Caspase-1/calpain cascade degraded filamin, enabling TF transport to MPs.
    • Caspase-1 facilitated actin exposure for MP release from filopodia.

    Conclusions:

    • A novel thromboinflammatory pathway initiated by extracellular ATP in macrophages was delineated.
    • This pathway involves inflammasome activation, TRX/TRXR system modulation, and TF-bearing MP generation.
    • Components of this pathway are potential therapeutic targets for treating inflammation and thrombosis.

    More Related Videos

    Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

    Evaluation of Caspase Activation to Assess Innate Immune Cell Death

    Published on: January 20, 2023

    4.0K
    Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation04:37

    Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation

    Published on: May 23, 2025

    1.3K

    Related Concept Videos

    Caspases01:24

    Caspases

    Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
    14.7K
    Extrinsic and Intrinsic Pathways of Hemostasis01:20

    Extrinsic and Intrinsic Pathways of Hemostasis

    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...
    15.9K
    The Extrinsic Apoptotic Pathway01:17

    The Extrinsic Apoptotic Pathway

    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...
    9.4K
    The Intrinsic Apoptotic Pathway01:31

    The Intrinsic Apoptotic Pathway

    Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
    9.3K
    Clot Retraction and Fibrinolysis01:16

    Clot 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.
    10.5K
    Anticoagulant Drugs: Low-Molecular-Weight Heparins01:30

    Anticoagulant Drugs: Low-Molecular-Weight Heparins

    Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
    2.6K