Scientists discover ‘patrol officers’ of the bloodstream

Our immune system protects the body from infections and helps repair damaged tissues. One of the cell types of the immune system is the macrophage, a type of white blood cell that acts as a ‘vacuum cleaner’ after an immune response. They engulf and break down bacteria, dead cells and other unwanted particles. In many tissues, macrophages act as local guards that keep an eye on their surroundings and quickly respond to danger. However, macrophages have never been observed in the human blood vessel network. Therefore, researchers of the Robin group set out to investigate whether the body has a dedicated group of macrophages that specifically guards the inside of the blood vessels.

Does the road network of the human body have guards?

Oxygen, immune cells, nutrients and waste constantly travel between organs through a network of blood vessels that connects the entire body, much like the roads we use to travel between destinations. Maintaining roads, clearing accidents and removing hazardous drivers from the road is essential to keep the traffic safe and moving smoothly. “These characteristics could also apply to the blood vessel network,” group leader Catherine Robin says.

Cells at work in real-time

For this investigation, the researchers used microscopy to visualize the blood vessels and blood in real time inside living zebrafish, which are transparent at early stages of development. The researchers injected foreign particles and cells with a fluorescent label into the bloodstream of zebrafish embryos. Thanks to this fluorescent label, they could follow the particles and cells inside the fish and observed that within 30 minutes, specific cells engulfed and cleared the particles. The researchers identified these cells as macrophages that actively patrol the bloodstream. In addition, the macrophages responded rapidly to injury in the vessel wall, suggesting that they also play an important role in maintaining the health and integrity of the blood vessels.

Unlike other immune cells that develop from specific immune cell precursors, the researchers found out that these macrophages originate from cells in the blood vessel lining. Blood vessels thus produce their own guardians. The researchers also found similar macrophages in mice, which could mean that the newly discovered type of macrophages exists in all mammals, including humans.

New questions

This discovery of this new macrophage type suggests that the immune system has a dedicated mechanism to protect the blood stream and raises many new research questions. How widespread is this protection mechanism? Do they function the same way in humans? And what role do they play in diseases? In the long run, the answers to these questions could provide insights into diseases in which blood vessels are damaged or inflamed, such as atherosclerosis and thrombosis.

The power of direct observation

This study highlights the power of directly observing biological processes. The use of live microscopy enabled the researchers to identify the macrophages. “With other techniques, we would likely have overlooked them entirely,” group leader Catherine Robin explains. The discoveries changed the long-held assumption in biology that all macrophages arise through the same developmental pathway. “Sometimes you have to see something before you know it exists,” Robin concludes.

Blood vessel-resident macrophages safeguard blood and vessel integrity in zebrafish. Credit: Bart Weijts, Jeroen Demmers, Catherine Robin. Copyright: Hubrecht Institute.

Publication

Blood vessel-resident macrophages safeguard blood and vessel integrity in zebrafish. Bart Weijts, Jeroen A. A. Demmers, Catherine Robin. Nature Immunology, 2026.