Human cells: Liquid retention triggers inflammation

For the first time, a research team discovered the connection between the filtering of tissue fluid in cells of the immune system and chronic inflammation.

Blocked filters in the cell: the cause of chronic inflammatory diseases?

For the first time, a research team discovered the connection between the filtering of tissue fluid in cells of the immune system and chronic inflammation.

Just as whales ingest huge amounts of water during their feeding process and then filter out their food, macrophages in our immune system also ingest large amounts of tissue fluid and then filter it in vacuoles inside the cells. During this filtration process, the cell must be able to release huge amounts of water, and also concentrate, digest and inspect the contents of the vacuoles in order to control the tissue and processes taking place.

A research team led by Dr. Stefan Uderhardt at the Friedrich–Alexander University Erlangen–Nürnberg (FAU), Germany, in cooperation with scientists in the USA, Canada, and Great Britain was able to decipher which biochemical processes regulate the water movements during filtration and thus keep the immune system in balance. The results of this study show a direct connection between basic cell biological processes and the development of inflammation.

In order to be able to protect our body effectively, defense cells, such as macrophages, must be in constant interaction with their environment. By continuously absorbing large amounts of tissue fluid and then filtering this fluid in vacuoles inside the cells, these cells are able to probe their environment with great precision and react quickly when threatened. However, the molecular mechanisms that enable the defense cells to regulate their fluid balance during this uptake process, and thus make the filtration function possible in the first place, were not known until now.

Using a combined approach of state-of-the-art microscopy technology and novel intravital imaging, the international research team succeeded in describing the molecular processes involved in isolated cell cultures and in living tissue. "We were able to identify specific channel-activating enzymes and electrolyte channels in immune cells which initiated the dissolution of vacuoles at key points of this cellular digestive system, and which are responsible for the monitoring function of tissue macrophages," said Dr. Stefan Uderhardt, head of the research group at the FAU’s Medical Clinic 3 for Rheumatology and Immunology. If these enzymes are missing or blocked by drugs, the tissue fluid cannot escape from the vacuoles, so the cell is "blocked" and its defense function is disturbed.

The results of these investigations showed for the first time a direct connection between basic cell biological processes such as the absorption and processing of tissue fluid and chronic inflammation. It appears that in disease situations such as lipid metabolism disorders, autoimmune diseases, and chronic inflammation, these molecular mechanisms may be disturbed, resulting in an increased risk of developing inflammatory diseases.

In the future, researchers will investigate to what extent disturbances in this "filter activity" are actually involved in the development of chronic inflammatory diseases, especially rheumatological diseases. The long-term goal is to develop potential approaches for innovative and targeted therapies for the prevention and treatment of inflammation.

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