Altered Human Neutrophil Function in Response to Acute Psychological Stress

Khanfer, Riyad; Phillips, Anna C.; Lord, Janet M.

doi:10.1097/psy.0b013e3181e7fae8

Cited by 26 publications

(18 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The neuroimmunoendocrine regulation of PrP C in neutrophils and its impact upon the cytotoxic potential of this cell may help explain previous observations that behavioral stress, which modifies both the risk and the course of various diseases (51)(52)(53)(54)(55) and strongly modulates the immune system (56 -58), also affects the cytotoxic functions of neutrophils (59). Notably, the cytotoxicity of neutrophils often swings toward the production of tissue damage (15,16).…”

Section: Discussionmentioning

confidence: 73%

“…Notably, the cytotoxicity of neutrophils often swings toward the production of tissue damage (15,16). This warrants the examination of the hypothesis that the neuroimmunoendocrine regulation of PrP C may be involved in the deregulation of vascular permeability concurrent with inflammatory components of various pathological conditions (16,59,(61)(62)(63). Interestingly, disruption of endothelial tight junctions also follows exposure to hydrogen peroxide (64,65).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Neuroimmunoendocrine Regulation of the Prion Protein in Neutrophils

Mariante

Nóbrega

Martins

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Prion protein (PrP C ) modulates inflammation, and prion diseases affect neutrophil numbers and functions, but the regulation of PrP C in neutrophils is unknown. Results: Inflammation and stress massively up-regulated PrP C in neutrophils via glucocorticoids and TGF-␤. Conclusion:We show a novel pathway of regulation of PrP C , with functional consequences for neutrophils. Significance: Systemic control of the expression and function of PrP C broadly modulates cellular physiology and pathology.The prion protein (PrP C ) is a cell surface protein expressed mainly in the nervous system. In addition to the role of its abnormal conformer in transmissible spongiform encephalopathies, normal PrP C may be implicated in other degenerative conditions often associated with inflammation. PrP C is also present in cells of hematopoietic origin, including T cells, dendritic cells, and macrophages, and it has been shown to modulate their functions. Here, we investigated the impact of inflammation and stress on the expression and function of PrP C in neutrophils, a cell type critically involved in both acute and chronic inflammation. We found that systemic injection of LPS induced transcription and translation of PrP C in mouse neutrophils. Up-regulation of PrP C was dependent on the serum content of TGF-␤ and glucocorticoids (GC), which, in turn, are contingent on the activation of the hypothalamic-pituitary-adrenal axis in response to systemic inflammation. GC and TGF-␤, either alone or in combination, directly up-regulated PrP C in neutrophils, and accordingly, the blockade of GC receptors in vivo curtailed the LPS-induced increase in the content of PrP C . Moreover, GC also mediated up-regulation of PrP C in neutrophils following noninflammatory restraint stress. Finally, neutrophils with upregulated PrP C presented enhanced peroxide-dependent cytotoxicity to endothelial cells. The data demonstrate a novel interplay of the nervous, endocrine, and immune systems upon both the expression and function of PrP C in neutrophils, which may have a broad impact upon the physiology and pathology of various organs and systems.

show abstract

Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Neuroimmunoendocrine Regulation of the Prion Protein in Neutrophils

Mariante

Nóbrega

Martins

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Kang et al (1997) found that examination stress increases superoxide production (1997). Acute psychological stress was reported to increase phagocytic ability and reduce superoxide production of neutrophils in humans (Khanfer et al, 2010), suggesting that the type of stress experienced has different effects on phagocytic abilities. Our current study did not distinguish between the contribution from neutrophil and monocyte/macrophage phagocytosis, which will be investigated later.…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports have shown that stress modulates neutrophil and macrophage recruitment, chemokine gene expression and the adhesion molecule expression (Curry et al, 2010; Filep et al, 1997; Heasman et al, 2003; Mizobe et al, 1997; Viswanathan and Dhabhar, 2005; Zhang et al, 1998). In addition, stress was reported to alter neutrophil and macrophage microbicidal functions (Ehrchen et al, 2007; Khanfer et al, 2010; Palermo-Neto et al, 2003). Previous studies in a murine model of cutaneous healing showed that restraint stress increased susceptibility to opportunistic infection.…”

Section: Introductionmentioning

confidence: 99%

Restraint stress alters neutrophil and macrophage phenotypes during wound healing

Tymen

Rojas

Zhou

et al. 2013

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

Previous studies reported that stress delays wound healing, impairs bacterial clearance, and elevates the risk for opportunistic infection. Neutrophils and macrophages are responsible for the removal of bacteria present at the wound site. The appropriate recruitment and functions of these cells are necessary for efficient bacterial clearance. In our current study we found that restraint stress induced an excessive recruitment of neutrophils extending the inflammatory phase of healing, and the gene expression of neutrophil attracting chemokines MIP-2 and KC. However, restraint stress did not affect macrophage infiltration. Stress decreased the phagocytic abilities of phagocytic cells ex vivo, yet it did not affect superoxide production. The cell surface expression of adhesion molecules CD11b and TLR4 were decreased in peripheral blood monocytes in stressed mice. The phenotype of macrophages present at the wound site was also altered. Gene expression of markers of pro-inflammatory classically activated macrophages, CXCL10 and CCL5, were down-regulated; as were markers associated with wound healing macrophages, CCL22, IGF-1, RELMα; and the regulatory macrophage marker, chemokine CCL1. Restraint stress also induced up-regulation of IL10 gene expression. In summary, our study has shown that restraint stress suppresses the phenotype shift of the macrophage population, as compared to the changes observed during normal wound healing, while the number of macrophages remains constant. We also observed a general suppression of chemokine gene expression. Modulation of the macrophage phenotype could provide a new therapeutic approach in the treatment of wounds under stress conditions in the clinical setting.

show abstract

“…In summary, acute stressors usually, with the exceptions of natural killer (NK) cell function (Cunnick et al 1988) and neutrophil superoxide production (Khanfer et al 2010(Khanfer et al , 2012, boost the immune system, particularly its innate component which is the one able to act quickly (Bosch et al 2003;Dhabhar and McEwen 1997;Sapolsky 1998). The majority of chronic stressors, on the other hand, are associated with global immunosuppression and have an impact on both innate and adaptive components of the immune system (Kiecolt- Glaser et al 1991a;Phillips et al 2006;Segerstrom and Miller 2004;Thaker et al 2006) to mention a few.…”

Section: Stress and The Immune Systemmentioning

confidence: 99%

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

Vitlić

Lord

Phillips

2014

AGE

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Altered Human Neutrophil Function in Response to Acute Psychological Stress

Cited by 26 publications

References 38 publications

Neuroimmunoendocrine Regulation of the Prion Protein in Neutrophils

Neuroimmunoendocrine Regulation of the Prion Protein in Neutrophils

Restraint stress alters neutrophil and macrophage phenotypes during wound healing

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

Contact Info

Product

Resources

About