LMU medical scientists discover new mechanism of alarmin release

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

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

The researchers report this in the journal Natural immunologythe release of these alarmins from the cell interior takes place via 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 prolonged activation. However, the LMU team, supported by partners in Germany and Switzerland, has now been able to demonstrate for the first time that pore formation and alarm release take place in the blood circulation and not just later in the tissue.

Fast and reversible pore formation

The research team also found that the process is not only fast, but also reversible. This means that the neutrophils can remove the formed pores within a few minutes. This prevents the cell death that would otherwise occur, 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 the possibility of therapeutically influencing inflammatory processes at a very early stage through modulation of the mechanisms involved in alarm release.


Ludwig Maximilian University of Munich (LMU)

Magazine 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. Natural immunology.

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