Intense physical exercise may lead to premature death of immune cells

Study of triathletes investigated the mechanisms that explain why neutrophils die sooner than they should.

By Diego Freire  |  Agência FAPESP – Researchers have discovered that intense physical exercise can accelerate the apoptosis of immune system cells known as neutrophils.

Apoptosis is the process of programmed cell death. It is important to the balanced functioning of all biological organisms but can be harmful to health if it is poorly regulated, as when tumor cells persist instead of dying naturally.

“Various cells in our organism need to die at certain intervals so they can be replaced by others. This is the case with neutrophils, which only last a certain time in the bloodstream because new neutrophils are continuously being produced in the bone marrow as part of a balanced physiological process that will be impaired if apoptosis is diminished,” said Tania Cristina Pithon Curi, a professor affiliated with the Center of Biological & Health Sciences at Universidade Cruzeiro do Sul in São Paulo, Brazil, and a participant in the project “Effects of regular physical activity on quality of life, stress levels and immune system in adults”, which was supported by FAPESP.

Neutrophils are a type of white blood cells, or leukocytes, that protect the organism against bacteria, viruses and other pathogens. A low neutrophil count exposes the organism to infection. This is what happened to 12 triathletes who took part in the study.

Shortly after some four hours of trials, during which they covered 21 km on foot, biked 90 km and swam 2 km, the athletes’ blood was sampled by the researchers in tent laboratories at the meet venue in Ubatuba on the coast of São Paulo State. Before competing, they had all had a complete checkup, including body composition and cardiorespiratory capacity assessments.

Neutrophils were isolated from the blood samples and analyzed for apoptosis on the basis of several parameters using a flow cytometer, a laser-based device that counts and sorts cells in terms of their physical and chemical properties.

“When a cell starts to die by apoptosis, a phospholipid called phosphatidylserine, which is present in the cell membrane, migrates to the external surface of the membrane. We treated the samples with a substance that binds to this phospholipid and emits a fluorescence that is detected by the cytometer,” Curi said.

“We also observed other typical traits of apoptosis, such as DNA fragmentation and alterations in mitochondria, that suggest the premature death of these cells, which normally survive in the bloodstream for approximately 10 hours.”

Therapeutic options

To investigate the possible causes of neutrophil apoptosis after intense physical exercise, the researchers looked for a link between the increased self-destruction of these cells and the plasma levels of free fatty acids, organic compounds produced by lipolysis, the breakdown of fat.

“Aerobic exercise boosts lipolysis, whereby lipids are broken down into glycerol and free fatty acids. One role of fatty acids in the metabolism is energy production. The presence of free fatty acids in large amounts due to exacerbated lipolysis may be associated with premature neutrophil apoptosis,” Curi said.

The researchers are now working on possible therapies to combat the loss of neutrophils in high-performance athletes.

“Physical exercise is of course positive and important, but as shown by these research findings regarding premature neutrophil apoptosis, it can also have negative effects depending on its intensity and frequency,” Curi said.

“Nevertheless, professional athletes can’t be asked simply to reduce their activities, so we’re investigating supplementation strategies capable of minimizing premature apoptosis. The goal is to prevent the debilitation of the immune system after intense exercise, which results in vulnerability to infection, among other hazards.”

One of the supplements studied is glutamine, a free amino acid that is the preferred fuel source for many types of immune cells.

“Glutamine is a non-essential amino acid produced by the organism as required. When an athlete performs very intense activities, his or her plasma concentration may be reduced, so supplementation can be important,” Curi said.

“When we investigated the molecular effect of this amino acid, which is significant for the function of leukocytes, we found that lymphocytes and monocytes consume glutamine at high rates. Neutrophils actually consume it more than glucose: the latter is consumed at a rate of 460 nanomoles/hour/mg protein, while the rate for glutamine is 770, almost 70% higher.”

According to Curi, glutamine may be responsible for “keeping cell machinery in proper working order, modulating cell function, and hence preventing apoptosis.”