Navigation Links
Ashwell receptor reduces mortality during sepsis
Date:5/18/2008

In research that solves the longest-standing mystery in glycobiology a field that studies complex sugar chains called glycans researchers at the University of California, San Diego School of Medicine have discovered that a molecule in the liver of all animals, called the Ashwell receptor, is critical in helping the body fight off the abnormal and lethal blood clotting caused by bacterial infection. Until now, it was suspected that this receptor might serve to remove abnormal proteins from circulation, but it wasnt understood which proteins were affected or what biological purpose this receptor served.

The study, published online in advance of publication in the June issue of Nature Medicine, shows that the Ashwell receptor plays an essential role in reducing coagulation abnormalities during infection and sepsis, significantly improving the probability of survival.

Sepsis, a life-threatening complication of bacterial infection in the blood, remains a major cause of death worldwide, according to the studys principal investigator, Jamey Marth, Ph.D., UCSD Professor of Cellular and Molecular Medicine and Investigator with the Howard Hughes Medical Institute. One of the major factors contributing to death in patients with sepsis is a condition called disseminated intravascular coagulation, which accelerates blood clotting.

UCSD researchers discovered that a protective response, triggered by the Ashwell receptor in the liver, limits this lethal side effect by reducing the levels of circulating blood coagulation factors, including platelets.

The bacterial pathogen Streptococcus pneumoniae (pneumococcus) is a leading cause of sepsis, especially in the young, the elderly and the immuno-compromised. The pneumococcus makes an enzyme called sialidase, which removes sugar molecules called sialic acid from host cells, and helps facilitate spread of the pathogen through the body. Using a mouse model of sepsis, the researchers found that the pneumococcal sialidase also removes sialic acid from circulating host factors involved in blood coagulation, including platelets and a glycoprotein called von Willebrand Factor (vWF). When this occurs, the Ashwell receptor recognizes the change in the glycoprotein structure and removes those pro-coagulation factors from circulation before they can cause increased blood coagulation.

The researchers made a breakthrough when they discovered that platelet counts and vWF that are reduced during pneumococcal infection remained high and unchanged in the absence of the Ashwell receptor. Pivotal results came when mice lacking the Ashwell receptor developed severe tissue and organ damage due to increased coagulation and died at significantly higher frequency and more rapidly than expected.

This finding contradicts the prevailing notion that the low platelet count of sepsis is due to the consumption of coagulation factors caused by the pathogen and is therefore harmful, said Marth. Rather, this low platelet count is due an adaptive response by the Ashwell receptor that is beneficial by reducing tissue damage and organ failure and thereby improving the chance of survival.

More than 35 years ago, researcher Gilbert Ashwell and colleagues discovered that the liver controls the removal of proteins in the bloodstream. The Ashwell receptor also known as the hepatic asialoglycoprotein receptor was the first glycan-binding receptor, or lectin, ever discovered in animals.

The Ashwell receptor is turned on after birth, and this was a clue that it is needed for environmental and pathogenic challenges, said Marth.

This research provides a whole new way of thinking about coagulation problems in sepsis produced by pneumococcus and related pathogens said Victor Nizet, M.D., UCSD professor of pediatrics and pharmacy whose laboratory assisted in the study. Drugs designed to support the normal capabilities of the Ashwell receptor in the liver would represent a new approach to limiting mortality in these life-threatening conditions.


'/>"/>

Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

Related medicine news :

1. Investigational Agent Targeting Metabotropic Glutamate 2/3 Receptors Demonstrates Antipsychotic Activity in Humans, Study in Nature Medicine Finds
2. Low level of neuronal receptor linked to mild cognitive impairment and Alzheimers disease
3. Pathway Diagnostics Announces Commercial Availability of SensiTrop(TM) HIV Co-receptor Tropism Assay
4. Pharmacopeia Acquires Selective Androgen Receptor Modulator (SARM) Program from Bristol-Myers Squibb
5. Food restriction increases dopamine receptor levels in obese rats
6. Quest Diagnostics Licenses Technology Underlying SensiTrop(TM) HIV Co-Receptor Tropism Test from Pathway Diagnostics
7. Abbott Researchers Target Neuronal Nicotinic Receptors for Treatment of Pain and Cognition
8. Exelixis to Receive Milestone Payment From Bristol-Myers Squibb for Achievement of Liver X Receptor Agonist Development Milestone
9. Receptor protein appears to be key in breakdown of kidney filtration
10. Cell-death receptor links cancer susceptibility and inflammation
11. Food peptides activate bitter taste receptors
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/16/2017)... ... January 16, 2017 , ... Houston dentist, Dr. Behzad ... offering complimentary consultations and financing for orthodontics for a limited time. Complimentary for ... learn about their orthodontic options. Walk-in, late-evening, Saturday, and same-day appointments are available. ...
(Date:1/16/2017)... ... ... well-aware of the following facts at present:, Flu and cold ... effect on keeping this particularly bad strain of the flu away , In ... , These facts are well-known among the team at Woodard! About halfway ...
(Date:1/16/2017)... ... January 16, 2017 , ... San Francisco dentist, Dr. Ben ... in 3-D scanning device which is capable of taking digital impressions of teeth and ... such as CAD CAM restorations , in terms of speed, efficiency and patient ...
(Date:1/15/2017)... ... ... is announcing the release of an updated version of their top selling clipper, the ... wide jaws that will accommodate nails up to 4mm in thickness . Nails like ... reinforced for extra strength when pressing down on dense nails which can be a hindrance ...
(Date:1/15/2017)... , ... January 15, 2017 , ... The Gravity Vault ... in Radnor, Pennsylvania. As construction wraps up on the 14,000+ square foot climbing gym, ... Vaults sixth location, including three in New Jersey and two in New York. With ...
Breaking Medicine News(10 mins):
(Date:1/16/2017)... Jan. 16, 2017  Today, Analytics 4 Life (A4L), ... announced its expansion into JLABS @ Toronto ... science incubators. As a resident in the space, A4L ... device development and commercialization expertise. JLABS @ ... innovation center that provides a flexible environment for start-up ...
(Date:1/15/2017)... , January 16, 2017 Le conseil ... à base de collagène pour la régénération de tissus humains, ... poste de directeur général avec effet immédiat. ... Bill est un dirigeant ... occupé plusieurs postes de gestion générale et de direction au ...
(Date:1/13/2017)... Stock-Callers is currently reviewing the following Medical Appliances ... WMGI ), Varian Medical Systems Inc. (NYSE: VAR ... NuVasive Inc. (NASDAQ: NUVA ). These companies belong ... finish on Thursday, January 12 th , 2017, with the ... health care companies in the S&P 500 were down less ...
Breaking Medicine Technology: