Navigation Links
New strategies against bird flu
Date:4/17/2008

The Spanish flu outbreak of 1918 killed between 30 and 50 million people. In the infected patients, the ultimate cause of death was acute respiratory distress syndrome (ARDS). This fatal condition is a massive reaction of the body during which the lung becomes severely damaged. ARDS can be induced by various bacterial and viral infections, but also by chemical agents. These could be toxic gases that are inhaled or gastric acid when aspirated. Once ARDS has developed, survival rates drop dramatically. Among patients infected with H5N1 bird flu, about 50 percent die of ARDS.

An international team of scientists has been addressing the underlying disease mechanisms for the past five years. The team involved researchers from leading institutions in Vienna, Stockholm, Cologne, Beijing, Hongkong, and Toronto as well as the US-army at Fort Detrick. The international effort was coordinated by Josef Penninger and Yumiko Imai of the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences.

A first breakthrough came in 2005 when IMBA-scientists identified ACE2 as the essential receptor for SARS virus infections and showed that ACE2 can protect from acute lung failure in disease models (Imai et al. Nature 2005; Kuba et al. Nature Medicine 2005). Based on these data, ACE2 is now under therapeutic development.

In a paper published by Cell this week, the authors describe an essential key injury pathway that is operational in multiple lung injuries and directly links oxidative stress to innate immunity. They also report for the first time a common molecular disease pathway explaining how diverse non-infectious and infectious agents such as anthrax, lung plague, SARS, and H5N1 avian influenza may cause severe and often lethal lung failure with similar pathologies.

To identify these pathways, the researchers studied numerous tissue samples from deceased humans and animals. Victims of bird flu and SARS were examined in Hongkong, and the US-army provided samples from animals infected with Anthrax and lung plague. Common to all ARDS samples was the massive amount of oxidation products found within the cells. Based on these findings, the scientists showed that oxidative stress is the common trigger that ultimately leads to lung failure.

To elucidate the entire pathway, Yumiko Imai of IMBA developed several mouse models. She was now able to show that a molecule called TLR4 (Toll-like receptor 4) is responsible for initiating the critical signalling pathway. TLR4 is displayed at the surface of certain lung cells called macrophages, important players of the bodys immune system. Once activated, TLR4 initiates an entire chain reaction which ends with the fatal failure of the lungs. Surprisingly, mice challenged with inactivated H5N1 avian influenza virus also dveloped the full reaction. On the other hand, mutant mice in which the function of TLR4 was genetically impaired were protected from lung failure in repsonse to the inactivated virus.

Based on these findings, the researchers can now outline a common molecular disease pathway: Microbial or chemical lung pathogens trigger the oxidative stress machinery. Oxidation products are intrepreted as danger-signals by the receptor TLR4. Subsequently, the bodys innate immune system is activated. This defense machinery in turn leads to a chain of reactions with severe and often fatal lung damage as a consequence.

For Yumiko Imai, a Postdoc in Josef Penningers team and pediatrician by training, these results are highly satisfying. Her motivation to study ARDS is based on personal experience in over 10 years at a pediatric intensive care unit. I have seen so many children die from acute lung failure and felt utterly helpless, Imai says. Since we found a common injury pathway, our hopes are high that we may be able to develop a new and innovative strategy for tackling severe lung infections.


'/>"/>

Contact: Dr. Heidemarie Hurtl
hurtl@imp.ac.at
43-179-730-3625
Research Institute of Molecular Pathology
Source:Eurekalert

Related biology news :

1. Conservation strategies must shift with global environmental change, says CU-Boulder study
2. Sea otter study reveals striking variability in diets and feeding strategies
3. NXG Strategies Launches Nations First Website Dedicated to Red Flag Compliance
4. A genetic identity card for Plasmodium populations to improve control strategies
5. New book presents successful strategies for probing genetic variation
6. Researchers discover new strategies for antibiotic resistance
7. Researchers discover critical detail of cellular defense against genetic mistakes
8. Standard chemo works better against metastatic BRCA1/2 breast cancer than against sporadic tumors
9. Evidence now suggests eating soy foods in puberty protects against breast cancer
10. Rare genetic mutations protect against hypertension
11. Researcher discovers pathway plants use to fight back against pathogens
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/6/2017)... Jan. 6, 2017  Privately-held CalciMedica, Inc., announced ... healthy volunteers of a novel calcium release-activated calcium ... pancreatitis. Acute pancreatitis, sudden painful ... disorder, but can be very serious.  In severe cases ... where extended hospital stays, time in the ICU ...
(Date:1/3/2017)... VEGAS , Jan. 3, 2017 Onitor, ... the introduction of Onitor Track, an innovative biometric data-driven ... men, showcasing this month at the 2017 Consumer Electronics ... In the U.S., the World Health ... more than two-thirds of adults who are overweight or ...
(Date:12/19/2016)... , España y TORONTO , 19 de ... con Northern Biologics Inc. que permitirá el desarrollo acelerado de MSC-1, ... clínicos en varios tipos de tumor en 2017, con múltiples sitios ... ... su clase con objetivo en el factor inhibidor de leucemia (LIF), ...
Breaking Biology News(10 mins):
(Date:1/18/2017)... NJ (PRWEB) , ... January 18, 2017 , ... ... to more and more E&L expertise. Within Albany Molecular Research, Inc. (AMRI), the ... in the past year and is planned for further growth in 2017. Extractable ...
(Date:1/18/2017)... ... 18, 2017 , ... BidMed, LLC, announced it will hold a ... lab equipment from two different leading institutes. This highly specialized laboratory equipment is coming ... States. This 1-day online auction will take place on BidMed’s website http://www.bidmed.com ...
(Date:1/18/2017)... Jan. 18, 2017  Caris Life Sciences, a ... Foundation, the largest private funder of pancreatic cancer ... evaluating the impact of immunotherapy in the treatment ... enrollment services to identify potential trial candidates based ... treating physicians and study investigators. The Lustgarten Foundation ...
(Date:1/17/2017)... YORK , Jan. 17, 2017 ... grow at a CAGR of around 7.5% over ... by 2025. Some of the prominent trends that ... growing incidences of diseases & graft transplant surgeries ... on Material the market is categorized into immunomodulatory ...
Breaking Biology Technology: