We’ve found a new way to fight harmful inflammation
A team of Scripps Research Institute identified the cause of excessive inflammation in the body by looking at immune cells. The findings open new doors to treating inflammation-related conditions.
In mammals, they make up about two-thirds of white blood cells present in our blood. Therefore, they have the role engulf invading microbes. Effectively, they release anti-microbial molecules through a process called “exocytosis”.
Proteins discovered in neutrophils could be a target to counter inflammation. In effectby an imaging technique called STORMresting neutrophils can be seen.
Treatments based on the WASH protein complex
the WASH protein complex forms a clustered molecular complex with microfilaments called F-actin and granular cargo near the plasma membrane. This study emphasizes the importance of multiprotein WASH who acts early in the fight against the excessive inflammatory activity of neutrophils. Thus, its absence facilitates the secretion of toxic granules and leads to systemic inflammation.
“Our results raise the possibility of future treatments targeting this WASH-regulated pathway to inhibit neutrophil-mediated inflammation while preserving most of neutrophil antimicrobial efficacy.”
Sergio Catz, the lead author of the study
Many antimicrobial molecules released by neutrophils can harm health. By exocytosis, the excessive release of these molecules leads to certain pathologies. Examples include sepsis, arthritis, lung injury, and inflammatory bowel disease. More extreme cases can also arise from this, such as cancer and atherosclerosis. The latter often causes heart attacks as well as strokes.
They used state-of-the-art cell biology approaches
There are two types of exocytosis. The first is to release “gelatinase granules” when there is any sign of infection or inflammation. The second starts uniquely in more severe cases by releasing “azurophile granules”. These the latter are more powerful and more likely to damage neighboring cells.
Scientists have discovered that WASH restricts the release of these toxic cargoes. Tested on mice, the presence of toxic azurophile molecules in their blood presented a rate three times higher mortality than normal mice.
“In this study, using state-of-the-art cell biology approaches, we revealed how neutrophils control their timely response through sequential exocytosis, and we identified a molecular system that acts as the gatekeeper to this process.”
However, scientists still have their work cut out for them to fully understand how exocytosis works. Now, Catz and his colleagues are continuing to study WASH and the molecules involved in this process. Also, they are trying to find drug molecules capable of stopping the excess production of azurophile granules. This task is not easy, because the functions of neutrophils as the first immune defense must be taken into account.