-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
iNature heparin is a mammalian polysaccharide, an anticoagulant widely used in the treatment of thrombotic diseases.
Heparin can improve the results of sepsis, which is the main cause of death due to immune dysfunction caused by infection.
Although it is relatively clear how heparin exerts its anticoagulant effect, the immune regulation mechanism that heparin can achieve is still a mystery.
On February 8, 2021, the Lu Ben team of Central South University published a research paper entitled "Heparin prevents caspase-11-dependent septic lethality independent of anticoagulant properties" in Immunity.
The study showed that heparin can prevent caspase- in sepsis.
11-dependent immune response and lethality, regardless of its anticoagulant properties.
Heparin or a chemically modified form of heparin without anticoagulant function inhibits the alarm protein HMGB1-lipopolysaccharide (LPS) interaction and prevents heparanase from degrading macrophage glycocalyxes.
These events prevented the cytoplasmic transmission of LPS in macrophages and the activation of caspase-11, a cytoplasmic LPS receptor that mediates the lethality of sepsis.
The survival rate of sepsis patients receiving heparin treatment is higher than that of patients not receiving heparin treatment.
The identification of this previously unrecognized function of heparin establishes a link between the innate immune response and blood coagulation.
Heparin is a mammalian polysaccharide with anticoagulant properties.
Since heparin was discovered in 1916 and first introduced into the clinic in the late 1930s, heparin has been widely used to treat various thrombotic diseases, such as venous thromboembolism.
Heparin exerts an anticoagulant effect by binding to lysine residues in antithrombin, thereby inducing irreversible conformational changes at the arginine reaction site.
This resulted in an increase in antithrombin activity by more than one hundred times.
In addition to thrombotic diseases, accumulated evidence from basic research and clinical practice also shows that heparin treatment can improve the efficacy of sepsis, which is the main cause of death, which is defined as a serious disease of organ dysfunction caused by infection.
Although it is assumed that heparin plays a beneficial role in sepsis through its anticoagulant properties, there is no consistent evidence to support this view.
Recent progress has shown that caspase-11 signaling plays a key role in the lethality of sepsis.
Caspase-11 is expressed in various types of cells, such as macrophages and endothelial cells.
After being activated by the main cell wall component of Gram-negative bacteria (lipopolysaccharide: LPS), caspase-11 cleaves gasdermin D (GSDMD) into peptides that form nanopores in the plasma membrane of the cell.
This event either leads to apoptosis, the lysed form of programmed cell death, or makes the cell hyperactive, releasing interleukin-1 (IL-1).
The formation of the GSDMD pore also triggers the systemic activation of the coagulation cascade, which leads to the lethality of sepsis.
Mechanistically speaking, calcium influx mediated by the GSMDD pore activates the transmembrane protein 16F (TMEMF16), which is a transmembrane phospholipase that can cause phosphatidylserine (PS) exposure.
In turn, this significantly enhances the procoagulant activity of tissue factor (TF) and the activation of the coagulation cascade.
High mobility group box 1 protein (HMGB1) promotes the activation of caspase-11 and GSDMD in endotoxemia or sepsis.
LPS triggers the release of HMGB1 from liver cells, which is the main source of plasma HMGB1 in sepsis.
Circulating HMGB1 binds to extracellular LPS and undergoes RAGE-dependent internalization through receptors, and then lysosome rupture induced by HMGB1 mediates the cytoplasmic delivery of LPS to the myeloid or endothelium In the cytoplasm of the cell, this ultimately leads to the activation of caspase-11 and the lysis of GSDMD.
Loss of HMGB1 in hepatocytes, neutralization of extracellular HMGB1, loss of caspase-11 or lack of GSDMD will uniformly improve the survival rate of experimental sepsis.
This study found that the polysaccharide motif of LPS is important for the HMGB1-LPS interaction.
As a mammalian polysaccharide, heparin can also physically interact with HMGB1.
The study found that heparin treatment improved the occurrence of sepsis by inhibiting caspase-11 signaling.
The minimum heparin dose effective to inhibit the caspase-11-dependent immune response is much lower than the minimum dose required to inhibit coagulation.
By using chemically modified non-anticoagulant heparin (NAH), it is shown that NAH treatment can prevent caspase-11-dependent diffuse intravascular coagulation (DIC) in sepsis.
In terms of mechanism, both heparin and NAH bind to HMGB1, inhibit the interaction of HMGB1-LPS, and prevent heparanase from degrading macrophage glycocalyx.
These events prevented the cytoplasmic transmission of LPS, resulting in reduced activation of caspase-11.
Therefore, this study determined the biological functions of heparin and provided a proof of concept that heparin can prevent caspase-11-dependent coagulation activation and lethality in sepsis, regardless of its direct anticoagulant properties.
Reference message: https://doi.
org/10.
1016/j.
immuni.
2021.
01.
007
Heparin can improve the results of sepsis, which is the main cause of death due to immune dysfunction caused by infection.
Although it is relatively clear how heparin exerts its anticoagulant effect, the immune regulation mechanism that heparin can achieve is still a mystery.
On February 8, 2021, the Lu Ben team of Central South University published a research paper entitled "Heparin prevents caspase-11-dependent septic lethality independent of anticoagulant properties" in Immunity.
The study showed that heparin can prevent caspase- in sepsis.
11-dependent immune response and lethality, regardless of its anticoagulant properties.
Heparin or a chemically modified form of heparin without anticoagulant function inhibits the alarm protein HMGB1-lipopolysaccharide (LPS) interaction and prevents heparanase from degrading macrophage glycocalyxes.
These events prevented the cytoplasmic transmission of LPS in macrophages and the activation of caspase-11, a cytoplasmic LPS receptor that mediates the lethality of sepsis.
The survival rate of sepsis patients receiving heparin treatment is higher than that of patients not receiving heparin treatment.
The identification of this previously unrecognized function of heparin establishes a link between the innate immune response and blood coagulation.
Heparin is a mammalian polysaccharide with anticoagulant properties.
Since heparin was discovered in 1916 and first introduced into the clinic in the late 1930s, heparin has been widely used to treat various thrombotic diseases, such as venous thromboembolism.
Heparin exerts an anticoagulant effect by binding to lysine residues in antithrombin, thereby inducing irreversible conformational changes at the arginine reaction site.
This resulted in an increase in antithrombin activity by more than one hundred times.
In addition to thrombotic diseases, accumulated evidence from basic research and clinical practice also shows that heparin treatment can improve the efficacy of sepsis, which is the main cause of death, which is defined as a serious disease of organ dysfunction caused by infection.
Although it is assumed that heparin plays a beneficial role in sepsis through its anticoagulant properties, there is no consistent evidence to support this view.
Recent progress has shown that caspase-11 signaling plays a key role in the lethality of sepsis.
Caspase-11 is expressed in various types of cells, such as macrophages and endothelial cells.
After being activated by the main cell wall component of Gram-negative bacteria (lipopolysaccharide: LPS), caspase-11 cleaves gasdermin D (GSDMD) into peptides that form nanopores in the plasma membrane of the cell.
This event either leads to apoptosis, the lysed form of programmed cell death, or makes the cell hyperactive, releasing interleukin-1 (IL-1).
The formation of the GSDMD pore also triggers the systemic activation of the coagulation cascade, which leads to the lethality of sepsis.
Mechanistically speaking, calcium influx mediated by the GSMDD pore activates the transmembrane protein 16F (TMEMF16), which is a transmembrane phospholipase that can cause phosphatidylserine (PS) exposure.
In turn, this significantly enhances the procoagulant activity of tissue factor (TF) and the activation of the coagulation cascade.
High mobility group box 1 protein (HMGB1) promotes the activation of caspase-11 and GSDMD in endotoxemia or sepsis.
LPS triggers the release of HMGB1 from liver cells, which is the main source of plasma HMGB1 in sepsis.
Circulating HMGB1 binds to extracellular LPS and undergoes RAGE-dependent internalization through receptors, and then lysosome rupture induced by HMGB1 mediates the cytoplasmic delivery of LPS to the myeloid or endothelium In the cytoplasm of the cell, this ultimately leads to the activation of caspase-11 and the lysis of GSDMD.
Loss of HMGB1 in hepatocytes, neutralization of extracellular HMGB1, loss of caspase-11 or lack of GSDMD will uniformly improve the survival rate of experimental sepsis.
This study found that the polysaccharide motif of LPS is important for the HMGB1-LPS interaction.
As a mammalian polysaccharide, heparin can also physically interact with HMGB1.
The study found that heparin treatment improved the occurrence of sepsis by inhibiting caspase-11 signaling.
The minimum heparin dose effective to inhibit the caspase-11-dependent immune response is much lower than the minimum dose required to inhibit coagulation.
By using chemically modified non-anticoagulant heparin (NAH), it is shown that NAH treatment can prevent caspase-11-dependent diffuse intravascular coagulation (DIC) in sepsis.
In terms of mechanism, both heparin and NAH bind to HMGB1, inhibit the interaction of HMGB1-LPS, and prevent heparanase from degrading macrophage glycocalyx.
These events prevented the cytoplasmic transmission of LPS, resulting in reduced activation of caspase-11.
Therefore, this study determined the biological functions of heparin and provided a proof of concept that heparin can prevent caspase-11-dependent coagulation activation and lethality in sepsis, regardless of its direct anticoagulant properties.
Reference message: https://doi.
org/10.
1016/j.
immuni.
2021.
01.
007
