Macrophage network in mouse tissue. Image credit: Tim Lämmermann
Macrophages are immune cells in the body that remove dying cells and debris from tissues. They live in almost all the body’s organs, surveilling for signs of infection and destroying microbes. They also migrate to wound sites, where they can eliminate foreign particles and stop microbes from entering the body.
To perform their surveillance role, macrophages need to work together as a team. They form a network, coordinating their movements to optimise the removal of particles and dead cells. How this happens is something of a mystery. As individuals, cells travel through tissues using a balance of several activities: they change their shape, they contract and relax, and they grab hold of their surroundings using proteins called integrins. It is thought that the choice between these types of movement may affect the rest of the network.
To investigate, Paterson and Lämmermann genetically engineered mouse macrophages grown in the laboratory so they would not produce working integrins. These macrophages were able to contract and relax, but they could not attach to the proteins in the structures they were exploring.
Paterson and Lämmermann then placed these macrophages in gels studded with proteins that mimic a biological matrix to observe their behaviour. When these macrophages were exposed to the chemicals that indicate the presence of a wound, they moved normally, changing shape and contracting and relaxing. Paterson and Lämmermann confirmed this normal behaviour for macrophages moving to sites of injuries in the tissue of living mice. However, when it came to surveillance, the macrophages’ abilities were seriously diminished, and they were unable to form an effective network to take up particles and dead cells.
This work sheds light on how the movement of individual cells affects the entire immune surveillance network. A deeper understanding could lead to new insights into how to prevent inflammation. The next step is to map macrophage networks in healthy and diseased tissues to understand how cell movement affects surveillance under different conditions.
