LMU medical scientists discover new mechanism of alarmin release

NewsGuard 100/100 Score

LMU medical scientists have demonstrated that important pro-inflammatory mediators are released into the bloodstream through tiny pores in the cell membrane at a very early stage of the immune response.

Many common illnesses such as arteriosclerosis and diabetes or neurodegenerative diseases such as Alzheimer's are associated with inflammatory processes. Gaining a better understanding of these processes is therefore an important stepping stone toward the development of new therapeutic approaches. Specific immune cells known as neutrophils play a decisive role in the initiation and maintenance of inflammatory processes in blood and tissue. In the course of their activation, these neutrophils already begin to release pro-inflammatory messengers into blood vessels, signaling to the body that the immune system must redouble its efforts. A team led by Professor Markus Sperandio at LMU's Institute of Cardiovascular Physiology and Pathophysiology has now discovered the molecular mechanisms by which neutrophils release certain messengers known as alarmins in a very early phase of the immune response.

As the researchers report in the journal Nature Immunology, the release of these alarmins from the cell interior occurs through gasdermin D pores in the cell membrane of the neutrophils, which are formed by activation of the so-called NLRP3 inflammasome. It was already known that immune cells can form these pores after extended periods of activation. However, the LMU team, supported by partners in Germany and Switzerland, has now been able to demonstrate for the first time that the pore formation and alarmin release take place in the blood circulation and not just later in the tissue.

Rapid and reversible pore formation

The research team also discovered that the process is not only fast, but reversible. That is to say, the neutrophils can remove the formed pores again in a matter of minutes. This prevents the cell death that would otherwise set in, as is often observed after activation of the NLRP3 inflammasome and subsequent pore formation.

The research thus expands our knowledge of how the NLRP3 inflammasome works and opens up the possibility of therapeutically influencing inflammatory processes at a very early stage through modulation of the mechanisms involved in alarmin release.

Source:
Journal reference:

Pruenster, M., et al. (2023). E-selectin-mediated rapid NLRP3 inflammasome activation regulates S100A8/S100A9 release from neutrophils via transient gasdermin D pore formation. Nature Immunology. doi.org/10.1038/s41590-023-01656-1.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Pregnant women show significant immune system changes linked to gut microbiome