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Research could lead to way to halt deadly immune response
Date:2/9/2010

ntire careers studying it, publishing in journals devoted solely to the study of this primordial defense mechanism.

The complement system exists in almost identical form in everything from seagulls to starfish. Its job is to launch a massive, multi-pronged attack against any foreign body that could threaten the life or health of an organism. Each method of attack is instigated by molecular changes involving as many as 30 substances that result in the same effect, a component designed to destroy the membrane encasing offending cells.

In the case of trauma that leaves cells without oxygen for too long, the complement system kicks in when the re-oxygenation occurs and lays waste to partially damaged cells that might otherwise survive. This is known as a reperfusion injury. This process kills slowly, often over several days. In heart attacks, the death of heart cells, cardiomyocytes, during reperfusion is irreversible and lethal. In cases of trauma and hypoxia, the progressive death of brain cells often results in catastrophic, irreversible brain injury or death. Multiple organ dysfunction syndrome caused by reperfusion injury is the leading cause of death in surgical patients and in trauma patients who survive the first 24 hours.

For decades, researchers have worked to develop medications and treatments to mitigate the effects of reperfusion injury.

Stopping the complement cascade could eliminate the major cause. In earlier published research, authors showed that the introduction of the harmless membrane of the coat of human astrovirus, which causes pediatric diarrhea, shuts down the main pathway leading to activation of an often lethal complement cascade. The research published in January's Molecular Immunology, demonstrates that the introduction of the astrovirus shell also shuts down a second major trigger, dubbed the lectin pathway.

"This research explains the almost complete cessation of complement activity," Krishna said. "This rapid cessati
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Contact: Doug Gardner
gardneda@evms.edu
757-446-6073
Eastern Virginia Medical School
Source:Eurekalert

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