Stressed to death: Implication of lymphocyte apoptosis for psychoneuroimmunology

Shi, Yufang; Devadas, Satish; Greeneltch, Kristy M.; Yin, Deling; Mufson, R. A.; Zhou, Jia‐Guo

doi:10.1016/s0889-1591(02)00062-4

Cited by 77 publications

(88 citation statements)

References 85 publications

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“…Although ADX eliminates GCs, it reduces epinephrine production as well. Catecholamines have apoptosis-inducing effects on lymphocytes (40,41), and it is possible that the higher lymphocyte numbers observed in ADX compared with Sham mice were due to overall lower epinephrine production. After ablation of the adrenal glands, circulating and tissue epinephrine levels may still be high because of extra-adrenal synthesis of epinephrine by methylation of norepinephrine via tissue phenylethanolamine N-methyltransferase (PMNT) (51).…”

Section: Discussionmentioning

confidence: 99%

Adrenalectomy in mice does not prevent loss of intestinal lymphocytes after exercise

Hoffman‐Goetz

Quadrilatero

Boudreau

et al. 2004

Journal of Applied Physiology

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Exhaustive exercise is associated with an increase in circulating glucocorticoids (GCs), lymphocyte apoptosis, and a reduction in intestinal lymphocyte number. The present study examined the role of GCs on the numerical changes seen in intestinal lymphocytes after exercise. Female C57BL/6 mice were bilaterally adrenalectomized (ADX; n ϭ 18) or given sham surgery (Sham; n ϭ 18) and assigned to one of three exercise conditions: treadmill running (28 m/min, 90 min, 2°slope) and killed immediately or after 24 h recovery, or not exercised and killed immediately after 90-min exposure to the treadmill environment. Lymphocytes were isolated from the intestines with CD45 ϩ cells collected by positive selection using magnetic bead separation columns, and lymphocyte subpopulations were analyzed by flow cytometry for CD45 ϩ , CD3␣␤ ϩ , CD3␥␦ ϩ , CD8␤ ϩ , CD8␣ ϩ , CD4 ϩ , and NK ϩ phenotypic markers. ADX mice had significantly more intestinal CD45 ϩ leukocytes (P Ͻ 0.05) and CD3␣␤ ϩ (P Ͻ 0.05), CD3␥␦ ϩ (P Ͻ 0.01), CD8␣ ϩ (P Ͻ 0.001), and NK ϩ (P Ͻ 0.05) intestinal lymphocytes than Sham mice. There was a significant effect of exercise condition on total intestinal CD45 ϩ leukocytes (P Ͻ 0.01) and CD3␣␤ ϩ (P Ͻ 0.05), CD8␣ ϩ (P Ͻ 0.001), and CD4 ϩ (P Ͻ 0.05) intestinal lymphocytes, with fewer cells at 24 h postexercise compared with the other treatment conditions. There were no surgical ϫ exercise interaction effects on the CD3 and CD8 phenotype numbers. Plasma corticosterone was virtually nil in ADX mice regardless of exercise condition but was significantly elevated in Sham mice immediately postexercise (P Ͻ 0.001). The data indicate that ADX does not prevent the loss of lymphocytes from the intestinal mucosa 24 h after strenuous exercise and GCs are not directly causal in the leukopenia of exercise. treadmill running; adrenal glands; glucocorticoids NUMEROUS STUDIES HAVE SHOWN that acute exercise is associated with induction of apoptosis or programmed cell death and loss of lymphocytes from blood, thymus, and spleen in humans and laboratory animals (9,20,28,29). Lymphocyte loss and/or apoptosis have been observed in other situations characterized by extreme physiological stress, including burn injury (15), electrical shock (48), and chronic restraint stress (42), and may reflect release of stress hormones, in particular glucocorticoids (GCs). GCs trigger apoptosis in lymphocytes by acting on an intracellular pathway via the mitochondria (2), which results in the accumulation of mitochondrial derived cytochrome c within the cytosol, loss of mitochondrial membrane integrity, externalization of phosphatidylserine at cell membranes, and DNA fragmentation (27,45).The intestinal intraepithelial lymphocytes (IELs) are a unique population of T cells that function as a first line of defense against exogenous pathogens, many of which develop independently of the thymus gland [i.e., T cells with the ␥␦ form of the T cell receptor (TCR)] (35). IELs play an important role in protection from epithelial tumor cells through their function a...

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Section: Discussionmentioning

confidence: 99%

Adrenalectomy in mice does not prevent loss of intestinal lymphocytes after exercise

Hoffman‐Goetz

Quadrilatero

Boudreau

et al. 2004

Journal of Applied Physiology

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“…For example, the suppression of mitogen responses by rat lymphocytes was dependent only upon the production of β-endorphin and without any influence by corticosterone levels (Panerai et al 1997). Similarly, Shi et al (2003) showed that the apoptosis of lymphocytes during restraint stress was dependent on the state of opioid receptors only. The adrenergic receptor (β 2 -AR) after binding catecholamines through two different signalling pathways triggers DNA damage as well as degradation of an important tumour suppressor in the brain of rats (Hara et al 2011).…”

Section: Stress and The Immune Systemmentioning

confidence: 98%

Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system

Vitlić

Lord

Phillips

2014

AGE

100

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The immune response is essential for keeping an organism healthy and for defending it from different types of pathogens. It is a complex system that consists of a large number of components performing different functions. The adequate and controlled interaction between these components is necessary for a robust and strong immune response. There are, however, many factors that interfere with the way the immune response functions. Stress and ageing now consistently appear in the literature as factors that act upon the immune system in the way that is often damaging. This review focuses on the role of stress and ageing in altering the robustness of the immune response first separately, and then simultaneously, discussing the effects that emerge from their interplay. The special focus is on the psychological stress and the impact that it has at different levels, from the whole system to the individual molecules, resulting in consequences for physical health.

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“…HU was carried out as described by Belay, et al [47]; in this system, mice are suspended by the tail using a strip of adhesive surgical tape that is attached to a chain hanging from a pulley, such that only the forelimbs touch the floor. The pulley suspension allows freedom of movement laterally while maintaining a [25][26][27][28][29][30] o angle between the longitudinal body axis and Apoptosis is an evolutionarily conserved 'cell suicide' program present in all nucleated metazoan cells [28][29][30]. Despite its highly conserved nature, it is only recently that some of the molecular mechanisms underlying apoptosis have been identified [31].…”

Section: Hindlimb Unloadingmentioning

confidence: 99%

“…We have now observed a similar loss of cellularity in mice after hindlimb unloading (HU), a ground-based animal model simulating some conditions of space flight. In these experiments, mice were suspended by tail traction (body axis at [25][26][27][28][29][30] o angle with cage floor) so that only the forelegs contacted the floor. Controls were housed under identical conditions, with the tail taped, but not suspended.…”

Section: Hindlimb Unloading (Hu) Causes Severe Depletion Of Lymphocytmentioning

confidence: 99%

Lymphocyte reduction induced by hindlimb unloading: distinct mechanisms in the spleen and thymus

et al. 2003

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Hindlimb unloading (HU) in rodent is a well-accepted ground-based model used to simulate some of the conditions of space flight and reproduce its deleterious effects on the musculoskeletal, cardiovascular and immune systems. In this study, the effects of HU on lymphocyte homeostasis in the spleen and thymus of mice were examined. HU was found to drastically deplete various cell populations in the spleen and thymus. These changes are likely to be mediated by apoptosis, since DNA strand breaks indicative of apoptosis were detected by terminal deoxynucleotidyl transferase-mediated nick end-labeling in both splenocytes and thymocytes. Surprisingly, administration of opioid antagonists or interference with the Fas-FasL interaction was able to block HU-induced reductions of splenocytes, but not thymocytes. On the other hand, steroid receptor antagonists blocked the reduction of lymphocyte numbers in both spleen and thymus. Therefore, the effects of HU on the homeostasis of splenocytes and thymocytes must be exerted through distinct mechanisms.

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Stressed to death: Implication of lymphocyte apoptosis for psychoneuroimmunology

Cited by 77 publications

References 85 publications

Adrenalectomy in mice does not prevent loss of intestinal lymphocytes after exercise

Adrenalectomy in mice does not prevent loss of intestinal lymphocytes after exercise

Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system

Lymphocyte reduction induced by hindlimb unloading: distinct mechanisms in the spleen and thymus

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