Related Experiment Video
Updated: May 26, 2026
07:08
Assessment of the Anticoagulant and Anti-inflammatory Properties of Endothelial Cells Using 3D Cell Culture and Non-anticoagulated Whole Blood
Published on: September 5, 2017
Thrombomodulin links coagulation to inflammation and immunity
1Division of Hematology, Stanford University School of Medicine, 269 Campus Drive, CCSR 1155, MC5156, Stanford, CA 9435-5156, USA. jmorser@stanford.edu
Current Drug Targets
|December 31, 2011
Summary
Thrombomodulin (TM) is a glycoprotein that regulates blood clotting and inflammation by binding thrombin. Its unique structure and functions are crucial for maintaining pregnancy and preventing excessive coagulation.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Thrombomodulin (TM) is a membrane glycoprotein with a C-type lectin domain, epidermal growth factor-like (EGF) motifs, and a glycosaminoglycan chain.
- TM modulates thrombin's activity, shifting it from procoagulant and pro-inflammatory to anticoagulant and anti-inflammatory roles through protein C (PC) and thrombin-activatable fibrinolysis inhibitor (TAFI) activation.
- The lectin domain of TM can bind high mobility group box protein 1 (HMGB1) and Lewis Y, acting as an antagonist to HMGB1 and conferring anti-inflammatory properties.
Purpose of the Study:
- To elucidate the structural and functional aspects of Thrombomodulin (TM) in regulating coagulation and inflammation.
- To understand the molecular interactions between TM, thrombin, and other binding partners like HMGB1.
- To highlight the physiological roles of TM in pregnancy, coagulation, and immune tolerance.
Main Methods:
- Analysis of the X-ray structure of thrombin bound to TM.
- Investigating the binding interactions of TM's domains (EGF 3-6, lectin domain) with thrombin and HMGB1.
- Evaluating the functional consequences of TM binding on thrombin's substrate specificity and immune cell activity.
Main Results:
- The X-ray structure reveals minimal alterations in thrombin's active site upon TM binding.
- Specific EGF domains (EGF4 for PC, EGF3 and EGF4 for TAFI, EGF5 and EGF6 for thrombin binding) are critical for TM's regulatory functions.
- TM's lectin domain antagonizes HMGB1, and TM treatment induces tolerogenic properties in dendritic cells.
- TM is essential for maintaining pregnancy and lifelong coagulation homeostasis.
- Soluble TM has been developed as an approved anticoagulant for disseminated intravascular coagulation.
Conclusions:
- Thrombomodulin (TM) is a multifunctional protein critical for anticoagulant and anti-inflammatory responses.
- TM's distinct domains mediate specific interactions, leading to profound modulation of thrombin activity and immune cell function.
- TM plays indispensable roles in physiological processes and has therapeutic potential as an anticoagulant.
Related Concept Videos
01:30Anticoagulant 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...
01:20Extrinsic 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 forms a...
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 forms a...
01:24Disorders of Hemostasis
Hemostasis, the process that stops bleeding after a blood vessel injury, is crucial for maintaining the integrity of the circulatory system. However, disorders of hemostasis can disrupt this delicate balance, leading to either excessive clotting or bleeding. These disorders can be broadly classified into thromboembolic disorders and bleeding disorders.
Thromboembolic Disorders
Two factors primarily cause thromboembolic conditions.
Thromboembolic Disorders
Two factors primarily cause thromboembolic conditions.
01:09Coagulation
The coagulation phase is a critical part of the body's process to prevent blood loss following injury to blood vessels. It involves chemical reactions that form a clot to seal the injured area. The clotting process begins shortly after injury, within 15-20 seconds for severe damage and 1-2 minutes for minor injuries.
During the coagulation phase, clotting factors, or procoagulants, play a vital role in initiating and progressing the coagulation cascade. This cascade is a series of reactions...
During the coagulation phase, clotting factors, or procoagulants, play a vital role in initiating and progressing the coagulation cascade. This cascade is a series of reactions...
01:06Coagulation
Colloidal solids are solid particles suspended in solution. They are usually negatively charged, attracting a compact primary layer of positively charged ions, which attract more counterions to form an electrical double layer. Electrostatic repulsion between the charged double layers prevents the particles from colliding, stabilizing the colloids. These solids are often undesirable because they can contain toxins that are difficult to remove. Coagulation is a technique that helps aggregate and...
01:28Inflammatory Response
An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...