Neuroimmunoendocrine Regulation of the Prion Protein in Neutrophils

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2012 Aug 23

PMID 22910907

Citations 16

Authors

Rafael M Mariante

Alberto Nobrega

Rodrigo A P Martins

Romulo B Areal

Maria Bellio

Rafael Linden

Affiliations

Soon will be listed here.

Abstract

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-β 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-β, 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 up-regulated 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.

Citing Articles

Prion protein alters viral control and enhances pathology after perinatal cytomegalovirus infection.

Karner D, Kvestak D, Kucan Brlic P, Cokaric Brdovcak M, Lisnic B, Brizic I Nat Commun. 2024; 15(1):7754.

PMID: 39237588 PMC: 11377837. DOI: 10.1038/s41467-024-51931-4.

Wnt, glucocorticoid and cellular prion protein cooperate to drive a mesenchymal phenotype with poor prognosis in colon cancer.

Mouillet-Richard S, Gougelet A, Passet B, Brochard C, Le Corre D, Pitasi C J Transl Med. 2024; 22(1):337.

PMID: 38589873 PMC: 11003154. DOI: 10.1186/s12967-024-05164-0.

Microglia in Prion Diseases: Angels or Demons?.

Peggion C, Stella R, Lorenzon P, Spisni E, Bertoli A, Massimino M Int J Mol Sci. 2020; 21(20).

PMID: 33092220 PMC: 7589037. DOI: 10.3390/ijms21207765.

Goats without Prion Protein Display Enhanced Proinflammatory Pulmonary Signaling and Extracellular Matrix Remodeling upon Systemic Lipopolysaccharide Challenge.

Salvesen O, Reiten M, Kamstra J, Bakkebo M, Espenes A, Tranulis M Front Immunol. 2017; 8:1722.

PMID: 29270176 PMC: 5723645. DOI: 10.3389/fimmu.2017.01722.

Prion protein is required for tumor necrosis factor α (TNFα)-triggered nuclear factor κB (NF-κB) signaling and cytokine production.

Wu G, Mu T, Gao Z, Wang J, Sy M, Li C J Biol Chem. 2017; 292(46):18747-18759.

PMID: 28900035 PMC: 5704461. DOI: 10.1074/jbc.M117.787283.

References

Satoh J, Kurohara K, Yukitake M, Kuroda Y . Constitutive and cytokine-inducible expression of prion protein gene in human neural cell lines. J Neuropathol Exp Neurol. 1998; 57(2):131-9. DOI: 10.1097/00005072-199802000-00004. View

Linden R, Cordeiro Y, Lima L . Allosteric function and dysfunction of the prion protein. Cell Mol Life Sci. 2011; 69(7):1105-24. PMC: 11114699. DOI: 10.1007/s00018-011-0847-7. View

Ballerini C, Gourdain P, Bachy V, Blanchard N, Levavasseur E, Gregoire S . Functional implication of cellular prion protein in antigen-driven interactions between T cells and dendritic cells. J Immunol. 2006; 176(12):7254-62. DOI: 10.4049/jimmunol.176.12.7254. View

Gunther E, Strittmatter S . Beta-amyloid oligomers and cellular prion protein in Alzheimer's disease. J Mol Med (Berl). 2009; 88(4):331-8. PMC: 2846635. DOI: 10.1007/s00109-009-0568-7. View

Rangel A, Madronal N, Gruart A, Gruart I Masso A, Gavin R, Llorens F . Regulation of GABA(A) and glutamate receptor expression, synaptic facilitation and long-term potentiation in the hippocampus of prion mutant mice. PLoS One. 2009; 4(10):e7592. PMC: 2763346. DOI: 10.1371/journal.pone.0007592. View

Scholz M, Cinatl J, Schadel-Hopfner M, Windolf J . Neutrophils and the blood-brain barrier dysfunction after trauma. Med Res Rev. 2006; 27(3):401-16. DOI: 10.1002/med.20064. View

Durig J, Giese A, Schulz-Schaeffer W, Rosenthal C, Schmucker U, Bieschke J . Differential constitutive and activation-dependent expression of prion protein in human peripheral blood leucocytes. Br J Haematol. 2000; 108(3):488-95. DOI: 10.1046/j.1365-2141.2000.01881.x. View

Pfeffer K, Matsuyama T, Kundig T, Wakeham A, Kishihara K, Shahinian A . Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell. 1993; 73(3):457-67. DOI: 10.1016/0092-8674(93)90134-c. View

NALBANDIAN R, Murayama M, Henry R . Restoration of phagocytosis and oxidative metabolism by Piracetam in failing human neutrophils: a qualitative assessment. Clin Immunol Immunopathol. 1983; 28(2):155-69. DOI: 10.1016/0090-1229(83)90150-2. View

10.

Cox G . Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes. J Immunol. 1995; 154(9):4719-25. View

11.

Trottier M, Newsted M, King L, Fraker P . Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function. Proc Natl Acad Sci U S A. 2008; 105(6):2028-33. PMC: 2538876. DOI: 10.1073/pnas.0712003105. View

12.

Westergard L, Christensen H, Harris D . The cellular prion protein (PrP(C)): its physiological function and role in disease. Biochim Biophys Acta. 2007; 1772(6):629-44. PMC: 1986710. DOI: 10.1016/j.bbadis.2007.02.011. View

13.

Paar C, Wurm S, Pfarr W, Sonnleitner A, Wechselberger C . Prion protein resides in membrane microclusters of the immunological synapse during lymphocyte activation. Eur J Cell Biol. 2007; 86(5):253-64. DOI: 10.1016/j.ejcb.2007.03.001. View

14.

Martins V, Beraldo F, Hajj G, Lopes M, Lee K, Prado M . Prion protein: orchestrating neurotrophic activities. Curr Issues Mol Biol. 2009; 12(2):63-86. View

15.

Borregaard N . Neutrophils, from marrow to microbes. Immunity. 2010; 33(5):657-70. DOI: 10.1016/j.immuni.2010.11.011. View

16.

Vere C, Streba C, Streba L, Ionescu A, Sima F . Psychosocial stress and liver disease status. World J Gastroenterol. 2009; 15(24):2980-6. PMC: 2702105. DOI: 10.3748/wjg.15.2980. View

17.

McGregor B, Antoni M . Psychological intervention and health outcomes among women treated for breast cancer: a review of stress pathways and biological mediators. Brain Behav Immun. 2008; 23(2):159-66. PMC: 2660328. DOI: 10.1016/j.bbi.2008.08.002. View

18.

Silva M . When two is better than one: macrophages and neutrophils work in concert in innate immunity as complementary and cooperative partners of a myeloid phagocyte system. J Leukoc Biol. 2010; 87(1):93-106. DOI: 10.1189/jlb.0809549. View

19.

Smith E, Batuman O, Trost R, Coplan J, Rosenblum L . Transforming growth factor-beta 1 and cortisol in differentially reared primates. Brain Behav Immun. 2002; 16(2):140-9. DOI: 10.1006/brbi.2001.0629. View

20.

Splettstoesser W, Schuff-Werner P . Oxidative stress in phagocytes--"the enemy within". Microsc Res Tech. 2002; 57(6):441-55. DOI: 10.1002/jemt.10098. View