Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein prevents detrimental immune effects of bacterial sepsis

23.05.2005


The anti-inflammatory protein annexin 1 may protect patients from the detrimental effects of severe inflammatory response syndrome, as reported by researchers at Barts and the London, Queen Mary’s School of Medicine and Dentistry. The paper by Damazo et al., "Critical protective role for annexin 1 gene expression in the endotoxemic murine microcirculation," appears in the June issue of The American Journal of Pathology and is accompanied by a commentary.



Severe inflammatory response syndrome, or SIRS, occurs when the body’s response to an overwhelming infection becomes uncontrolled. The very immune response meant to clear the pathogen and its toxins actually causes damage to the host’s own tissues when it goes into overdrive, releasing too many immune signals. Thus, the immune response must be carefully controlled to prevent damage to the host.

Damazo et al. studied this balancing act by analyzing the effects of the bacterial toxin LPS on normal and annexin 1 knockout mice. Annexin 1 was chosen because it appears to be involved in the resolution phase of the immune response: its expression on white blood cells impairs their ability to bind blood vessel walls, preventing their transit from the blood to other organs.


When normal mice were treated with LPS, the immune system induced a steady migration of white blood cells from the blood into affected tissues. However, mice deficient for annexin 1 exhibited a dramatic release of white blood cells from blood vessels, ultimately leading to 100% mortality by 48 hours.

The researchers characterized the expression of annexin 1 and found that the gene was activated as early as 1.5 and 6 hours after LPS administration, with levels returning to normal by 24 hours. Higher levels of markers of inflammation, and of organ injury, were measured in annexin 1 deficient animals. Altogether, these findings implied that the protective effects of the annexin 1 pathway were activated in the first few hours following toxin administration. In fact, when annexin 1 knockout mice were given small doses of human recombinant annexin 1 in the first 24 hours following LPS treatment, survival increased to 60%.

These results, obtained in the lab of Dr. Mauro Perretti, highlight the delicate balance between the "pro-inflammatory/detrimental vs. anti-inflammatory/protective phases" of the immune response. Dr Perretti explained, "For too long, we have ignored anti-inflammatory/counter-regulatory mediators and the impact they have on pathology outcome; studying the way our body controls responses to infections can allow the modeling of new therapeutics with lower side effects."

The importance of this work is underscored by the fact that bacterial sepsis ranked among the top ten causes of death in both adults and neonates in 2002 in the United States (Natl Vital Stat Rep 2005, 53:1-89). The patients at greatest risk of developing sepsis and SIRS are those with impaired immune systems. When such patients are unable to control the underlying bacterial infection, their immune systems overcompensate and trigger a dangerous cascade of tissue damage.

Thus, to prevent death from sepsis, physicians must not only control the bacterial infection but better control the detrimental effects of the immune system. Dr. Perretti’s lab is further investigating these immune pathways: "The ultimate goal is to use these new targets (e.g., a receptor for a given anti-inflammatory mediator) to develop better and safer drugs." The data for annexin 1 provide a new direction for such therapeutics that delicately balances removal of bacterial toxins and damage to host tissues.

Siân Wherrett | EurekAlert!
Further information:
http://www.qmul.ac.uk

More articles from Life Sciences:

nachricht Chips, light and coding moves the front line in beating bacteria
16.08.2018 | Okinawa Institute of Science and Technology (OIST) Graduate University

nachricht Protein droplets keep neurons at the ready and immune system in balance
16.08.2018 | Howard Hughes Medical Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Diving robots find Antarctic seas exhale surprising amounts of carbon dioxide in winter

16.08.2018 | Earth Sciences

Protein droplets keep neurons at the ready and immune system in balance

16.08.2018 | Life Sciences

3D inks that can be erased selectively

16.08.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>