Acute exercise stimulates macrophage function: possible role of NF‐κB pathways

Abstract

Moderate physical activity when performed on a regular basis presents a number of benefits to the whole organism, especially regarding immune system function, such as augmenting resistance to infections and to cancer growth. Although glutamine production by active muscle cells as well as neuroendocrine alterations mediated by the chronic adaptation to exercise may play a role, the entire mechanism by which exercise makes the immune system aware of challenges remains mostly uncovered. This is particularly true for the effects of an acute exercise session on immune function. In this work, circulating monocytes/macrophages from sedentary rats submitted to an acute (1 h) swimming session were tested for the ability of phagocytosing zymosan particles, phorbol miristate acetate (PMA)-induced hydrogen peroxide production, nitric oxide (NO) release (assessed by nitrate and nitrite production) and the expression of NO synthases (NOS-1, NOS-2 and NOS-3). The results showed that an exercise bout induced a 2.4-fold rise in macrophage phagocytic capacity (p ¼ 0.0041), a 9.6-fold elevation in PMA-induced hydrogen peroxide release into the incubation media (1-h, p ¼ 0.0022) and a 95.5%-augmentation in nitrite basal production (1-h incubation; p ¼ 0.0220), which was associated with a marked expression of NOS-2 (the inducible NOS isoform; p ¼ 0.0319), but not in other NOS gene products. Although NOS-2 expression is nuclear factor-kB (NF-kB)-dependent, no systemic oxidative stress was found, as inferred from the data of plasma TBARS and glutathione disulphide (GSSG) to glutathione (GSH) ratio in circulating blood erythrocytes which remained constant after the acute exercise. Also, no stressful situation seemed to be faced by monocytes/macrophages, since the expression of the 70-kDa heat shock protein (HSP70) remained unchanged. We conclude that NF-kB-dependent induction of NOS-2 and macrophage activation must be related to local factor(s) produced in the surroundings of monocytes/macrophages.

Glutamine supplementation prevents exercise‐induced neutrophil apoptosis and reduces p38 MAPK and JNK phosphorylation and p53 and caspase 3 expression

“…9,10 Exercise mobilizes peripheral immune cells and the magnitude of this effect reflects the intensity and duration of the effort. 11,12 Intense training increases the susceptibility to infections 9 and this may result from impairment in neutrophil function or acceleration in the process of neutrophil death. 13 Short-term exhaustive exercise or intensive treadmill exercise is known to induce DNA damage in lymphocytes in 14 Recently, we have demonstrated that a single session of exercise induces DNA fragmentation and mitochondrial membrane depolarization, increases expression of pro-apoptotic genes (bax and bcl-xS) and decreases expression of anti-apoptotic genes (bcl-xL) in rat neutrophils.…”

The role of exercise on the innate immunity of the elderly

“…The response depends on the intensity, duration and mode of exercise, changes in body temperature, blood flow, hydration status and body position concentrations of hormones and cytokines. The cells showing more responsiveness to the effects of acute exercise, both in terms of numbers and function, are NK cells, neutrophils and macrophages [60]. Instead, helper T-cell counts and other immune measures are not enhanced significantly.…”

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

“…Following that, physical exercise, which is the most powerful physiological inducer of iHSP70 expression, compared only to heat stress and fever-related conditions [34,[46][47][48], is considered, at the same time, the best solution to unfasten this perceived Gordian knot (an intractable problem that may be solved by "thinking outside the box") of senescence-associated chronic inflammatory diseases, as recently suggested [7]. In addition to that, several studies have reported that the amino acid L-glutamine (thereafter referred to as glutamine) strongly enhances the HS response by acting as a potentializer of iHSP70 expression [49,50], mainly via the hexosamine biosynthetic pathway (HBP) [51][52][53][54][55][56].…”