Related Experiment Video

Updated: May 13, 2026

Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
11:40

Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature

Published on: April 1, 2014

Dysfunction of endothelial protein C activation in severe meningococcal sepsis

S N Faust1, M Levin, O B Harrison

  • 1Department of Paediatrics, Imperial College School of Medicine at St Mary's Hospital, London, United Kingdom.

The New England Journal of Medicine
|August 11, 2001
PubMed

Insights

Impaired protein C pathway function, indicated by reduced thrombomodulin and protein C receptor expression, contributes to thrombosis in severe meningococcal sepsis. This down-regulation of the endothelial protein C system hinders anticoagulation.

Area of Science:

  • Hematology
  • Vascular Biology
  • Pediatric Infectious Diseases

Background:

  • Impaired protein C anticoagulation pathway is crucial in sepsis-associated thrombosis and purpura fulminans.
  • Severe meningococcal sepsis involves thrombosis and purpuric lesions.

Purpose of the Study:

  • To investigate the expression of thrombomodulin and the endothelial protein C receptor in the dermal microvasculature of children with severe meningococcal sepsis.
  • To correlate these findings with the integrity of the endothelium and the protein C pathway activation.

Main Methods:

  • Biopsy specimens of purpuric lesions from 21 children with meningococcal sepsis were analyzed.
  • Expression of thrombomodulin and endothelial protein C receptor was assessed via electron microscopy.
  • Plasma levels of protein C pathway components were measured and compared to controls.

Main Results:

  • Endothelial thrombomodulin and protein C receptor expression were significantly lower in sepsis patients compared to controls.
  • Endothelial cells were generally intact, suggesting impaired function rather than damage.
  • Plasma levels of protein C, protein S, and antithrombin were reduced, while plasma thrombomodulin was elevated in sepsis patients.

Conclusions:

  • Severe meningococcal sepsis is characterized by impaired protein C activation.
  • This impairment is linked to the down-regulation of the thrombomodulin-endothelial protein C receptor pathway.
  • Findings highlight a critical mechanism in meningococcal sepsis pathogenesis.
Abstract

More Related Videos

Inducing Meningococcal Meningitis Serogroup C in Mice via Intracisternal Delivery10:03

Inducing Meningococcal Meningitis Serogroup C in Mice via Intracisternal Delivery

Published on: November 5, 2019

Neisseria meningitidis Infection of Induced Pluripotent Stem-Cell Derived Brain Endothelial Cells10:12

Neisseria meningitidis Infection of Induced Pluripotent Stem-Cell Derived Brain Endothelial Cells

Published on: July 14, 2020

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...
Viral Meningitis01:18

Viral Meningitis

Viral meningitis is the most common form of meningitis and is often referred to as aseptic meningitis to indicate the absence of bacterial involvement. It is generally milder than bacterial meningitis, with symptoms including fever, headache, stiff neck, drowsiness, nausea, photophobia, and vomiting. Rarely, more severe manifestations or death may occur. Common causative agents include enteroviruses, particularly coxsackie A and B viruses and echoviruses, all members of the Enterovirus genus...
Bacterial Meningitis I: Introduction01:22

Bacterial Meningitis I: Introduction

Bacterial meningitis is a severe, life-threatening inflammation of the meninges, particularly the pia mater and arachnoid mater, affecting the subarachnoid space, ventricles, and cerebrospinal fluid (CSF). If untreated, it can lead to significant neurological complications or death.Causative AgentsCommon pathogens vary with age and immune status. In adults, major organisms include Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Streptococcus agalactiae (group B...
Bacterial Meningitis II: Pathophysiology01:26

Bacterial Meningitis II: Pathophysiology

Bacterial meningitis typically begins when pathogens such as Neisseria meningitidis and Streptococcus pneumoniae colonize the nasopharynx and invade the bloodstream. This process is facilitated by bacterial virulence factors, such as polysaccharide capsules, which resist phagocytosis and complement-mediated killing. Less commonly, bacteria reach the central nervous system via contiguous spread from infections like otitis media or sinusitis, through congenital or acquired dural defects, or...
Cerebral Edema ll: Pathophysiology01:22

Cerebral Edema ll: Pathophysiology

Vasogenic edema is a major form of cerebral edema characterized by abnormal accumulation of fluid in the brain’s extracellular space due to disruption of the blood–brain barrier (BBB). The BBB is a specialized structure composed of endothelial cells connected by tight junctions, supported by astrocytic endfeet and a basement membrane. Under normal conditions, it tightly regulates the movement of ions, proteins, and solutes between the bloodstream and brain parenchyma. When this barrier loses...
Cytotoxic Edema: Pathophysiology01:21

Cytotoxic Edema: Pathophysiology

Cytotoxic edema is a form of cerebral edema characterized by intracellular swelling of neurons, astrocytes, and other glial cells. It develops when the mechanisms responsible for maintaining ionic gradients across the cell membrane become impaired. Under normal physiological conditions, the sodium–potassium ATPase actively transports sodium ions out of the cell and potassium ions into the cell, preserving osmotic balance and enabling electrical signaling. This pump requires a continuous supply...