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When the body encounters harmful stimuli,Inflammatory responseIt is an important means of protecting the body. In a balanced state, inflammation removes these harmful substances and initiates tissue repair. However, once the inflammatory response is excessive, it will lead to tissue damage and disease. In this process, variousImmune cellsThey play a key role and work together during inflammation. When faced with different harmful stimuli, the types of immune cells involved vary, which also affects the outcome of the inflammatory response.

in,Mast cellsMast cells are distributed around blood vessels and nerve endings in various tissues and are a type of immune cell that is crucial for initiating inflammatory responses. Mast cells are filled with granules containing pro-inflammatory substances, which are released when they encounter potential dangers, thereby causing inflammatory responses. Many people's mast cells also respond to seemingly harmless environmental factors, which act as allergens and cause allergic reactions.How do mast cells interact with other immune cells at the site of an allergic reaction?This question remains largely unanswered.

In a study published in Cell, the Max Planck Institute ofimmunityA research team led by the Institute of Biology and Epigenetics used two-photon microscopy in vivo imaging to study the relationship between the expression of mitochondria and the growth of progenitor cells in living mouse tissues.ObservedThe real-time dynamic changes of mast cells and other cells activated during an allergic reaction. The research team was surprised to find thatThere are actually neutrophils among mast cells.

▲The latest research found that mast cells (brown) can attract and capture neutrophils (cyan) to form a cell-in-cell structure(Image credit: Marcus Frank & Karoline Schulz, Universitätsmedizin Rostock)

Neutrophils are the frontline defenders of the immune system, responding quickly to a wide range of potential threats. They circulate in the blood, and when inflammation occurs, they quickly move from the blood vessels to the site of inflammation. There, neutrophils can engulf invaders, release antimicrobial components, or form "neutrophil extracellular traps" to capture and killPathogens, to deal with foreign invasions such as bacteria and fungi.

However, most of what the scientific community knows about neutrophils comes from injuries andInfectmodel, but the role of neutrophils in inflammation caused by allergic reactions remains poorly understood.

▲Mast cells capture neutrophils in the body(Video source: Reference [1])

After observing neutrophils inside mast cells, the research team wanted to understand how and why mast cells capture neutrophils. To this end, the research team simulated the neutrophil capture phenomenon observed in living tissue in in vitro cell culture and identified the molecular pathways involved in this process. They found that mast cells release a protein calledLeukotriene B4Neutrophils often use these substances to initiate their own clustering response, that is, to gather together to kill pathogens.

By secreting leukotriene B4, mast cells attract neutrophils. Once neutrophils are close enough, mast cells engulf them into a vacuole, an intracellular structure called a, which the researchers call "Mast cell intracellular trap”。

Interestingly, neutrophils form snares made of DNA and histones to capture microorganisms during infection; however, under allergic conditions, they fall into the snares of mast cells.

▲The formation of mast cell intracellular traps depends on mast cell degranulation and the release of leukotriene B4(Video source: Reference [1])

The research team further confirmed that mast cell intracellular traps were also present in human samples. They also studied the fate of the two cell types involved after the capture and found that the captured neutrophils eventually died, but their undigested material remained in the mast cell vacuole for several days. The researchers pointed out thatMast cells can recycle materials from neutrophils to enhance their own function and metabolism. In addition, mast cells can delay the release of newly acquired neutrophil components, thereby triggering additional immune responses and helping to maintain inflammation and immune defense.

▲ Schematic diagram of the research mechanism(Image source: Reference [1])

"This new understanding of how mast cells and neutrophils work together adds a whole new dimension to our understanding of allergic reactions and inflammation. It suggests thatMast cells can use neutrophils to enhance their own capabilities, which may have implications for chronic allergies where inflammation recurs." says Professor Tim Lämmermann, who led the study. The researchers have already begun studying this interaction in human mast cell-mediated inflammatory diseases to see if this discovery could lead to new ways to treat allergic and inflammatory diseases.

References:

[1] Neutrophil trapping and nexocytosis, mast cell-mediated processes for inflammatory signal relay., Cell (2024). DOI: 10.1016/j.cell.2024.07.014