New Approach to Studying Immune Processes Developed

Scientists at the Centro Nacional de Investigadores Cardiovasculares (CNIC) have discovered that circulating neutrophils acquire different behavior patterns during inflammatory processes. Their study, published today in Nature, identifies a harmful neutrophil behavior associated with cardiovascular disease.  

Neutrophils form the first line of defense in the body but that can also damage healthy cells, including cells in the cardiovascular system. “Several studies have linked the presence of neutrophils in blood to a higher risk and severity of cardiovascular disease,” said first author Georgiana Crainiciuc. Nevertheless, Crainiciuc also pointed out that it is not possible to protect the cardiovascular system simply by removing neutrophils as this would “leave the body defenseless against any pathogen that threaten it.”  

To resolve this problem, the authors sought to identify the specific types of neutrophils that cause vascular injury. The researchers analyzed cells by high-resolution intravital microscopy, a technology that allows the visualization of cells within the blood capillaries of live animals.  

The scientists designed a computational system that allowed them to analyze how cells behave in vessels through simple measures of changes in size, shape, and movement. This analysis identified three neutrophil behavior patterns during inflammatory processes but showed that only one of them, characterized by large size and proximity to the vessel wall, is linked to cardiovascular injury.

Combining this computational system with massive genetic analysis in animal models, the authors were able to identify the molecules responsible for the harmful neutrophil behavior.  The team found that the cause of this pathological behavior is a single molecule, Fgr. This discovery should help in selecting highly effective drugs able to prevent inflammation and cell death after a myocardial infarction. “The idea now is to continue with further tests and analysis needed to convert this into a clinical treatment for patients,” added Crainiciuc.

The scientists believe that the study signals a major advance not only toward improved treatment of cardiovascular disease, but also in the methodology for analyzing immune cells. “With current techniques, researchers can analyze of a large number of genes and molecules per cell, and this has enabled the discovery of numerous cell populations associated with the development of disease,” explained co-first author Miguel Palomino-Segura.

Nevertheless, he added, “our model is unique because it allows the identification of cells not from their genetic profile but from their activity during a disease. This is a completely new approach to the study of immune processes that exploits the dynamism of the disease state to generate new information.”