Nav: Home

Identifying therapeutic targets in sepsis' cellular videogame

May 08, 2019

LEXINGTON, Ky. (May 8, 2019) -- Sepsis is a medical condition that few patients have heard of and most doctors dread. The body's response to attack by bacteria can trigger a cascade of cellular self-destruction that inadvertently causes blood clots, multi-organ failure, and death.

The immune system functions as a sort of cellular Pac-Man, using white blood cells to hunt out the "bad guys," initiating attacks and counter-attacks. However, in extreme cases, white blood cells commit a sort of hara-kiri, triggering their own death in an attempt to destroy the infection. Sometimes it works -- but when it doesn't, the complications are dangerous.

The arsenal of weapons to treat severe cases of sepsis is miserably small, and physicians have little to provide other than antibiotics, fluids, and hope. Exciting new research has defined the chain of molecular events that goes awry in sepsis, opening up opportunities for new treatments to fight the condition that affects more than a million Americans each year and kills up to a third of them.

Two collaborating laboratories at the University of Kentucky were able to establish the events within white blood cells that progresses from inflammasome activation to a type of programmed cell death called pyroptosis -- and culminates in the damaging blood clots.

"Recent studies have uncovered the mechanism of pyroptosis following inflammasome activation, but we didn't know how pyroptotic cell death drives the disease process," said Zhenyu Li, M.D., Ph.D., an associate professor in the University of Kentucky's Department of Molecular and Cellular Biochemistry.

"If we could uncover that link, it would open up possibilities for therapies that target inflammatory, infection-mediated clotting."

The teams, led by Li and Yinan Wei, Ph.D. of UK's Department of Chemistry, determined that certain bacterial proteins and endotoxin trigger inflammasome activation in white blood cells, causing pyroptosis. During pyroptosis, pores form in the white blood cell membrane that result in the release of tissue factor, a protein known to initiate the clotting process.

"Our data establish inflammasome activation as an important link between inflammation and blood clotting," Li said. "Our findings advance the understanding of the relationship between bacterial infections and coagulation as well as provide evidence that inflammasome may be a potential therapeutic target for sepsis."
-end-
The data was published online this week in advance of its June publication in Cell Press' Immunity.

University of Kentucky

Related Sepsis Articles:

Milestone for the early detection of sepsis
Researchers from Graz, Austria, are developing a ground-breaking method that uses biomarkers to detect sepsis 2 to 3 days before the first clinical symptoms appear.
Breast milk may help prevent sepsis in preemies
Researchers at Washington University School of Medicine in St. Louis and Mayo Clinic in Rochester, Minn., have found -- in newborn mice -- that a component of breast milk may help protect premature babies from developing life-threatening sepsis.
Finding a new way to fight late-stage sepsis
Researchers have developed a way to prop up a struggling immune system to enable its fight against sepsis, a deadly condition resulting from the body's extreme reaction to infection.
Study: Sepsis survivors require follow-up support
Survivors of sepsis -- a life-threatening response to an infection -- have expressed a need for advocacy and follow-up support, according to a study authored by professors at the University of Tennessee, Knoxville, and the University of Tennessee Health Science Center in Memphis, and published in Dimensions of Critical Care Nursing.
After decades of little progress, researchers may be catching up to sepsis
After decades of little or no progress, biomedical researchers are finally making some headway at detecting and treating sepsis, a deadly medical complication that sends a surge of pathogenic infection through the body and remains a major public health problem.
Study changes guidelines for sepsis management
University of Arizona Health Sciences researcher ends debate among physicians regarding sepsis management.
Improving outcomes for sepsis patients
More than 1 million sepsis survivors are discharged annually from acute care hospitals in the United States.
Genes linked to death from sepsis ID'd in mice
Bacteria in the bloodstream can trigger an overwhelming immune response that causes sepsis.
Identifying therapeutic targets in sepsis' cellular videogame
Exciting new research has defined the chain of molecular events that goes awry in sepsis, opening up opportunities for new treatments to fight the condition that affects more than a million Americans each year and kills up to a third of them.
New computer-aided model may help predict sepsis
Can a computer-aided model predict life-threatening sepsis? A model developed in the UK that uses routinely collected data to identify early symptoms of sepsis, published in CMAJ, shows promise.
More Sepsis News and Sepsis Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Processing The Pandemic
Between the pandemic and America's reckoning with racism and police brutality, many of us are anxious, angry, and depressed. This hour, TED Fellow and writer Laurel Braitman helps us process it all.
Now Playing: Science for the People

#568 Poker Face Psychology
Anyone who's seen pop culture depictions of poker might think statistics and math is the only way to get ahead. But no, there's psychology too. Author Maria Konnikova took her Ph.D. in psychology to the poker table, and turned out to be good. So good, she went pro in poker, and learned all about her own biases on the way. We're talking about her new book "The Biggest Bluff: How I Learned to Pay Attention, Master Myself, and Win".
Now Playing: Radiolab

Invisible Allies
As scientists have been scrambling to find new and better ways to treat covid-19, they've come across some unexpected allies. Invisible and primordial, these protectors have been with us all along. And they just might help us to better weather this viral storm. To kick things off, we travel through time from a homeless shelter to a military hospital, pondering the pandemic-fighting power of the sun. And then, we dive deep into the periodic table to look at how a simple element might actually be a microbe's biggest foe. This episode was reported by Simon Adler and Molly Webster, and produced by Annie McEwen and Pat Walters. Support Radiolab today at Radiolab.org/donate.