Researchers identify molecules responsible for dangerous neutrophil behavior

Researchers headed by Dr Andres Hidalgo of the Centro Nacional de Investigadores Cardiovasculares (CNIC) have found that circulating neutrophils—a kind of immune cell—acquire distinct behavior patterns during inflammatory processes. The research, which was published in Nature, discovered a potentially harmful neutrophil activity linked to cardiovascular disease.

Researchers identify molecules responsible for dangerous neutrophil behavior
Scientists at the CNIC have developed a simple model for studying the behavior of immune cells in live animals and have identified a harmful cell behavior pattern associated with cardiovascular disease. Image Credit: Centro Nacional de Investigadores Cardiovasculares.

The findings improve the understanding of myocardial infarction and potentially lead to new therapies.

Neutrophils are immune cells that act as the body’s first line of defense, but they can also cause harm to healthy cells, including those in the cardiovascular system.

Several studies have linked the presence of neutrophils in blood to a higher risk and severity of cardiovascular disease.”

Georgiana Crainiciuc, Study First Author, Centro Nacional de Investigadores Cardiovasculares

Crainiciuc noted that it is not possible to safeguard the cardiovascular system by eliminating neutrophils as this might “leave the body defenseless against any infection that threatens it.”

The team tried to identify the unique kinds of neutrophils that induce vascular damage to solve this problem. High-resolution intravital microscopy, a technique for visualizing cells within live animals’ blood capillaries, was used to study the cells.

The findings, which were published in Nature, might lead to the development of novel therapies that mitigate the consequences of myocardial infarction.

The researchers developed an extremely unique computational system that enabled them to examine how cells behave in vessels using simple measures of changes in shape, size, and movement. During inflammatory processes, three neutrophil behavior patterns were found, but only one of them, described by high size and proximity to the artery wall, was connected to cardiovascular damage, according to this study.

The Fgr molecule

The team was able to discover the molecules responsible for the dangerous neutrophil behavior by combining this computational method with extensive genetic analysis in animal models.

The researchers discovered that a single molecule, Fgr, is responsible for this unusual behavior. This breakthrough paves the way for the development of extremely effective therapies that can reduce inflammation and cell death following myocardial infarction. “The idea now is to continue with further tests and analysis needed to convert this into a clinical treatment for patients,” Crainiciuc explained.

The researchers believe the discovery represents a significant step forward not just in the treatment of cardiovascular disease, but also in the methods of evaluating 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.”

Dr Miguel Palomino-Segura, Study Co-First Author, Centro Nacional de Investigadores Cardiovasculares

Dr Miguel Palomino-Segura adds, “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.”

The key to this approach is the ability of neutrophils to change their shape, activity, and capacity to migrate in a matter of seconds. These rapid changes can only be captured under the microscope.”

Dr Andres Hidalgo, Centro Nacional de Investigadores Cardiovasculares

The researchers achieved this using high-resolution intravital microscopy, which allows them to see cells within living animals’ blood capillaries.

The study team worked with engineers from Universidad Carlos III de Madrid to create novel computer vision techniques for obtaining measurements in live tissues to completely exploit the potential of the pictures.

The study also needed extensive efforts to create the computing capacity required to integrate and analyze the large data systematically obtained from hundreds of cells. “This technology has been applied to other kinds of data, but this is the first example of its use to treat microscopy data, and the results have been surprising,” explained Jon Sicilia, co-author and bioinformatician in charge of the project’s analytical section.

The researchers anticipate that this innovative technique will be used in other fields of science.

The objective now is to adapt this technique in other scenarios, such as infection or cancer, where immune cells also play a vital role in disease development,” concludes Palomino-Segura.

Nature - Spanish scientists discover a cell behavior pattern that predicts cardiovascular disease

Scientists led by Dr Andres Hidalgo at the Centro Nacional de Investigadores Cardiovasculares (CNIC) have discovered that circulating neutrophils—a type of immune cell—acquire different behavior patterns during inflammatory processes. The study, published in Nature, identifies a harmful neutrophil behavior associated with cardiovascular disease. Video Credit: Centro Nacional de Investigadores Cardiovasculares.

Source:
Journal reference:

Crainiciuc, G., et al. (2022) Behavioral immune landscapes of inflammation. Nature. doi.org/10.1038/s41586-021-04263-y

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