Nav: Home

Scientists found means to inhibit capillary leakage in sepsis

June 25, 2018

Increased capillary permeability and subsequent leakage from the capillaries is associated with numerous difficult-to-cure diseases, including acute respiratory distress syndrome (ARDS), severe Dengue fever and malaria, and sepsis.

Currently, there is no effective therapy to inhibit capillary leakage and to maintain vessel stability in these diseases.

The latest research published in the Proceedings of the National Academy of Sciences of USA (PNAS) ,2,3 indicates that a monoclonal antibody targeted against β1-integrin inhibits vascular leakage in a mouse model of sepsis.

Integrins are heterodimeric cell surface receptors that mediate interactions between cells and the surrounding extracellular matrix. β1-integrin is a key molecule in endothelial cells, which form the inner layer of the blood vessel wall. Previously, β1-integrin has been known to regulate blood vessel formation and vessel stability. Scientists have now identified a novel function for β1-integrin in vascular leakage associated with severe inflammation and sepsis.

Principal investigator, Dr. Pipsa Saharinen, at the University of Helsinki and Wihuri Research Institute said:

"We made a remarkable discovery: a molecule that was previously known to mediate vessel stability, behaved in an opposite manner in inflammation, by inducing vessel destabilization and leakage. We found that inflammatory agents induced cell contractility that was mediated via β1-integrin, leading to gap formation between endothelial cells and increased permeability."


The scientists used a mouse model of gram-negative sepsis (also termed endotoxemia), which was induced in mice by a bacterial component (LPS). The scientists found that the antibody against β1-integrin bound to the vascular endothelium, improved the junctions between endothelial cells and decreased vascular leakage in sepsis. In addition, the antibody protected the mice from sepsis-induced heart failure.

The antibody against β1-integrin was effective as a prophylactic treatment, but also as an intervention therapy i.e. when the antibody was administered after the onset of the disease.

"This is important since it mimics more the situation in real life. Sepsis may develop unexpectedly and proceed fast. When the patients arrive at the hospital, the disease may have already progressed. It would be important to have the means to inhibit vessel leakiness and the development of a more severe disease. In our study, the antibody against β1-integrin was effective in inhibiting vascular leak in mice even when it was administered after the onset of the leakage", Dr. Saharinen said.

In sepsis the body's own inflammatory reaction becomes overwhelming. Due to the increased level of numerous inflammatory agents, it has been so far difficult to develop a targeted therapy for sepsis.

"Using endothelial cells in culture, we found that β1-integrin is a key mediator of not only one, but several inflammatory agents that are upregulated in sepsis. Furthermore, we found that a vascular growth factor Angiopoietin-2, which is known to play a role in the pathogenesis of sepsis, regulated β1-integrin signaling in endothelial cells. Although there is still a lot of work to do to, these exciting results could ultimately help us develop an effective treatment to block capillary leak in sepsis", Saharinen concluded.

University of Helsinki

Related Sepsis Articles:

Readily available drug cocktail can help prevent sepsis shock and death
Even in advanced medical settings, sepsis is still very dangerous and accounts for over 400,000 deaths annually in the US alone.
A rusty and sweet side of sepsis
A research team led by Miguel Soares at the Instituto Gulbenkian de Ciência (IGC) in Portugal discovered an unsuspected mechanism that is protective against sepsis.
New pediatric protocol reduces missed sepsis diagnoses by 76 percent
An electronic sepsis alert using a combination of vital signs, risk factors and physician judgment to identify children in a pediatric emergency department with severe sepsis reduced missed diagnoses by 76 percent.
Machine learning may help in early identification of severe sepsis
A machine-learning algorithm has the capability to identify hospitalized patients at risk for severe sepsis and septic shock using data from electronic health records (EHRs), according to a study presented at the 2017 American Thoracic Society International Conference.
Faster is better when it comes to sepsis care
An analysis covering nearly 50,000 patients from 149 New York hospitals is the first to offer scientific evidence that a controversial early sepsis care regulation worked.
Prompt sepsis treatment less likely when ERs overcrowded
According to a new study, patients with sepsis, a life-threatening complication of an infection, had delays approaching one hour in being given antibiotics when seen in emergency rooms that were overcrowded.
New test to rapidly diagnose sepsis
Researchers have developed a test that can rapidly and reliably diagnose sepsis, a potentially life-threatening complication of bacterial infections.
Children who survive sepsis often experience lingering effects
Survival rates have risen dramatically in recent years among children who develop sepsis, a severe, life-threatening immune reaction to an infection somewhere in the body.
Recognize sepsis as a separate cause of illness and death
Sepsis should be recognized as a separate cause of illness and death around the world.
Simple measures cut sepsis deaths nearly in half
Sepsis, also called blood poisoning, is a common affliction that can affect people of all ages.

Related Sepsis Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Moving Forward
When the life you've built slips out of your grasp, you're often told it's best to move on. But is that true? Instead of forgetting the past, TED speakers describe how we can move forward with it. Guests include writers Nora McInerny and Suleika Jaouad, and human rights advocate Lindy Lou Isonhood.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...