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Nat Med. 2014 Jul;20(7):754-758. doi: 10.1038/nm.3589. Epub 2014 Jun 22.

Chronic variable stress activates hematopoietic stem cells.

Author information

1
Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge St., Boston, MA 02114, USA.
2
Department of Cardiology and Angiology I, University Heart Center, Freiburg, Germany.
3
Division of Psychiatry and Medicine, Massachusetts General Hospital.
4
Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital.
5
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
6
Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
#
Contributed equally

Abstract

Exposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis. Although incompletely understood, interaction between the psyche and the immune system provides one potential mechanism linking stress and disease inception and progression. Known cross-talk between the brain and immune system includes the hypothalamic-pituitary-adrenal axis, which centrally drives glucocorticoid production in the adrenal cortex, and the sympathetic-adrenal-medullary axis, which controls stress-induced catecholamine release in support of the fight-or-flight reflex. It remains unknown, however, whether chronic stress changes hematopoietic stem cell activity. Here we show that stress increases proliferation of these most primitive hematopoietic progenitors, giving rise to higher levels of disease-promoting inflammatory leukocytes. We found that chronic stress induced monocytosis and neutrophilia in humans. While investigating the source of leukocytosis in mice, we discovered that stress activates upstream hematopoietic stem cells. Under conditions of chronic variable stress in mice, sympathetic nerve fibers released surplus noradrenaline, which signaled bone marrow niche cells to decrease CXCL12 levels through the β3-adrenergic receptor. Consequently, hematopoietic stem cell proliferation was elevated, leading to an increased output of neutrophils and inflammatory monocytes. When atherosclerosis-prone Apoe(-/-) mice were subjected to chronic stress, accelerated hematopoiesis promoted plaque features associated with vulnerable lesions that cause myocardial infarction and stroke in humans.

PMID:
24952646
PMCID:
PMC4087061
DOI:
10.1038/nm.3589
[Indexed for MEDLINE]
Free PMC Article
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