How Mast Cells Recruit Neutrophils to Inflammation Sites

How mast cells and neutrophils communicate has been unraveled by researchers at Otto-von-Guericke University who say their finding may allow for developing targeted therapeutic strategies to dampen allergic responses and inflammatory reactions. The results were published last month in Immunity.

The team set out to understand how TNF in tissue-resident mast cells was delivered to neutrophils circulating inside blood vessels. To do so, they employed high-resolution 2-Photon-Microscopy, which showed how mast cells position themselves, guardian-like, directly around the blood vessel and even insert protrusions into the vessel lumen. In case of emergency, granula containing TNF are released directionally from these protrusions. As a result, the TNF immediately is present where the neutrophils can "see" it—in the bloodstream, circulating through the vessels. The TNF activates surface proteins on the neutrophils. Then the cells become stickier, and can attach themselves at the vessel wall and migrate into the surrounding tissue.

"The capacity of mast cells to degranulate directionally into the blood stream might explain why local allergen encounter can trigger a systemic anaphylactic shock. Next, we want to understand the exact mechanisms mast cells use to insert these protrusions into the vessel wall. Targeting these might reveal therapeutic strategies to dampen allergic shock or cytokine storm syndromes. At the same time, it might also enable us to harness the ability of mast cells to stimulate the immune response, notably the recruitment of neutrophils, during infections," senior author Anne Dudeck explained.