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Related Concept Videos

Complement System01:27

Complement System

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 membrane...
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 forms a...
Acute Inflammation III: Local and Systemic Effects01:25

Acute Inflammation III: Local and Systemic Effects

Acute inflammation produces a coordinated set of local and systemic changes that limit injury, eliminate pathogens, and initiate repair. These responses arise within minutes of infection, trauma, or chemical insult and are driven by vascular alterations and leukocyte-derived mediators. When the stimulus resolves, the reaction typically abates within days.Local EffectsAt the site of injury, arteriolar vasodilation increases blood flow, resulting in redness and warmth. Simultaneously, increased...
Antimicrobial Proteins01:23

Antimicrobial Proteins

Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
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 cells.
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...

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Related Experiment Video

Updated: May 26, 2026

Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
05:28

Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis

Published on: December 9, 2022

The protein C pathway and sepsis.

Patrizia Della Valle1, Giulia Pavani, Armando D'Angelo

  • 1Coagulation Service & Thrombosis Research Unit, Scientific Institute San Raffaele, Milano, Italy.

Thrombosis Research
|December 14, 2011
PubMed
Summary

Activated protein C (APC) shows anti-inflammatory effects in severe sepsis. Its protective mechanisms, particularly via PAR-1, may be mimicked by administering protein C zymogen, offering a potential new sepsis therapy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Critical Care Medicine

Background:

  • The protein C (PC) pathway is crucial in regulating inflammation and coagulation.
  • Activated protein C (APC) demonstrated survival benefits in animal sepsis models.
  • APC's therapeutic effects in severe sepsis are attributed to anti-inflammatory and cytoprotective properties, not anticoagulation.

Purpose of the Study:

  • To investigate the protective mechanisms of APC in severe sepsis.
  • To elucidate the role of protease-activated receptor 1 (PAR-1) and endothelial protein C receptor (EPCR) in APC's signaling.
  • To explore the potential of using protein C zymogen as a therapeutic alternative to APC.

Main Methods:

  • Review of existing literature on APC signaling pathways.

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Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice

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Related Experiment Videos

Last Updated: May 26, 2026

Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
05:28

Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis

Published on: December 9, 2022

Cecal Ligation Puncture Procedure
11:53

Cecal Ligation Puncture Procedure

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  • Analysis of APC's interaction with EPCR and PAR-1.
  • Examination of thrombin's effect on PAR-1 and EPCR-bound endothelial cells.
  • Evaluation of studies involving h-PC zymogen administration in sepsis models.

    • Main Results:

    • APC exerts protective effects by binding EPCR and cleaving PAR-1, suppressing pro-inflammatory cytokines and apoptosis, and enhancing endothelial barrier function.
    • Thrombin also cleaves PAR-1 but can induce pro-inflammatory signaling.
    • Endothelial cell cultures show that thrombin-mediated PAR-1 cleavage can be anti-inflammatory and barrier-protective when EPCR is occupied by PC.
    • Animal sepsis models suggest that administering h-PC zymogen may recapitulate APC's beneficial effects.

    Conclusions:

    • APC's anti-inflammatory and cytoprotective actions are key in severe sepsis treatment.
    • The interplay between APC, thrombin, EPCR, and PAR-1 is complex but suggests a potential therapeutic window.
    • Administering protein C zymogen (h-PC) may offer a viable strategy to achieve APC-like protective effects in severe sepsis.