Immune advice: a way has been found to turn off inflammation in the body with blood proteins

Russian scientists have found that different blood proteins have different effects on the movement and properties of neutrophils, the key cells of the innate immune system. They are the first to react to infection or tissue damage, rapidly migrating from the bloodstream to the site of inflammation and destroying pathogens. The strength of the immune response largely depends on the speed and effectiveness of their work. The results obtained will be useful for developing new approaches to the diagnosis and treatment of various diseases, including sepsis, distress syndrome, and autoimmune pathologies. At the same time, experts note that in order to confirm the practical significance of the findings, the study must be tested in clinical trials.

Soldier cells on the body's defense

The scientists examined substances whose concentration in the blood varies with different diseases, such as fibrinogen (a protein of the acute phase of inflammation) and ceruloplasmin (a copper—containing protein of the acute phase). In the future, such studies will explore the mechanisms of the immune response and control it, for example, to enhance it in case of infections or, conversely, to reduce it in case of excessive inflammation. The work was attended by specialists from NUST MISIS, PIAF named after B. P. Konstantinov, Lomonosov Moscow State University, SPbPU and the A.A. Smorodintsev Influenza Research Institute.

— The university's specialists studied the behavior of neutrophils using an ion-conducting microscope, which makes it possible to track changes in living cells in real time without affecting them. In the NUST MISIS unique scanning facility, the experiment was brought closer to the conditions in which neutrophils work in the body. The results of the study will help to better understand how the body reacts to inflammation and protects itself from infections," said Alevtina Chernikova, Rector of NUST MISIS.

Scientists have experimentally confirmed that fibrinogen increases neutrophil motility, while ceruloplasmin has the opposite effect — it reduces the motility of immune cells.

The key result of the work was the understanding that proteins affect not only the speed of movement, but also the "rigidity" of cells — their mechanical properties. These parameters determine the ability of neutrophils to pass through tissues and perform their protective function.

— Interestingly, the reaction of the cells turned out to be different: groups of neutrophils with different movement speeds formed within the same sample. This confirms that immune cells can behave differently even under the same conditions," said Alexander Yerofeyev, PhD, Head of the NUST MISIS Laboratory of Biophysics.

The scientists' conclusions are important not only for fundamental science, but also for practical medicine. According to Vasily Kolmogorov, a research engineer at the university's biophysics laboratory, the levels of fibrinogen and ceruloplasmin vary in various diseases, so their effect on the behavior of neutrophils can be used to more accurately diagnose and assess the course of inflammatory processes.

"Gas" and "brake" for immunity

Neutrophils are important soldier cells that arrive en masse at the site of inflammation to fight infection, but they also often damage surrounding tissues, Mikhail Bolkov, a researcher at the Institute for the Study of Aging at the Russian Gerontological Research and Clinical Center at Pirogov University, told Izvestia. Usually, such injuries recover quickly and remain invisible to humans, but in severe inflammatory conditions they can lead to serious complications. According to the expert, the results of the study will certainly benefit in the treatment of such conditions.

— For example, ceruloplasmin or peptides based on it can be used to artificially increase the rigidity of neutrophils. This will stop their migration into tissues and help prevent systemic organ damage, for example, in acute respiratory distress syndrome or sepsis," the scientist said.

Neutrophils are the first to recognize infection or tissue damage and rush into the focus to destroy pathogens, noted molecular biologist Arina Kholkina. But balance is important here: if there are too many of them and they are too active, healthy tissues are damaged. If they are not enough or they are slow, the infection spreads. Regulating the movement of these cells means controlling inflammation.

— Scientists have discovered that two blood proteins work like a gas pedal and a brake pedal. Fibrinogen makes neutrophils more flexible and accelerates them by almost one and a half times. Ceruloplasmin, on the contrary, stiffens the cells and slows them down, preventing them from leaving the vessels to the site of inflammation. In different diseases, the level of these proteins changes, which means that the behavior of neutrophils also changes," said Arina Kholkina.

In the future, these proteins can be targeted: to accelerate neutrophils in case of prolonged infections or, conversely, to slow them down in case of sepsis and cytokine storm, protecting organs from destruction, the expert believes. The effect of therapy will become more predictable, because the doctor will manage not the inflammation in general, but a specific link in the immune response.

At the same time, experts note that further clinical studies are needed to confirm the findings.