Document Detail


Neurokinin-1 receptor (NK1-R) expression in the brains of SIV-infected rhesus macaques: implications for substance P in NK1-R immune cell trafficking into the CNS.
MedLine Citation:
PMID:  20671267     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent studies suggest a link between neuropsychiatric disorders and HIV/SIV infection. Most evidence indicates that monocytes/macrophages are the primary cell type infected within the CNS and that they contribute to CNS inflammation and neurological disease. Substance P (SP), a pleotropic neuropeptide implicated in inflammation, depression, and immune modulation via interaction with its cognate receptor, the neurokinin 1 receptor (NK1-R), is produced by monocyte/macrophages. While the presence of NK1-R on neurons is well known, its role on cells of the immune system such as monocyte/macrophages is just beginning to emerge. Therefore, we have examined the expression of SP and NK1-R and their relationship to SIV/HIV encephalitis (SIVE/HIVE) lesions and SIV-infected cells. These studies demonstrated intense expression of SP and NK1-R in SIVE lesions, with macrophages being the principal cell expressing NK1-R. Interestingly, all of the SIV-infected macrophages expressed NK1-R. Additionally, we examined the functional role of SP as a proinflammatory mediator of monocyte activation and chemotaxis. These studies demonstrated that treatment of monocytes with SP elicited changes in cell-surface expression for CCR5 and NK1-R in a dose-dependent manner. Moreover, pretreatment with SP enhanced both SP- and CCL5-mediated chemotaxis. All of these findings suggest that SP and NK1-R are important in SIV infection of macrophages and the development of SIVE lesions.
Authors:
Heather Vinet-Oliphant; Xavier Alvarez; Elizabeth Buza; Juan T Borda; Mahesh Mohan; Pyone P Aye; Florin Tuluc; Steven D Douglas; Andrew A Lackner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-07-29
Journal Detail:
Title:  The American journal of pathology     Volume:  177     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-31     Completed Date:  2010-12-13     Revised Date:  2011-09-13    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1286-97     Citation Subset:  AIM; IM    
Affiliation:
Tulane National Primate Research Center, Division of Comparative Pathology, Covington, LA 70433, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Astrocytes / immunology,  metabolism,  virology
Brain / immunology,  metabolism*,  virology
Cell Movement
Cells, Cultured
Flow Cytometry
Immunohistochemistry
Macaca mulatta
Macrophages / immunology,  metabolism,  virology
Microscopy, Confocal
Neurons / immunology,  metabolism,  virology
Receptors, Neurokinin-1 / immunology,  metabolism*
Simian Acquired Immunodeficiency Syndrome / immunology,  metabolism*,  virology
Simian immunodeficiency virus / immunology*
Substance P / immunology,  metabolism*
Grant Support
ID/Acronym/Agency:
MH076388/MH/NIMH NIH HHS; NS30769/NS/NINDS NIH HHS; RR000164/RR/NCRR NIH HHS; RR016930/RR/NCRR NIH HHS; RR018397/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Neurokinin-1; 33507-63-0/Substance P
Comments/Corrections

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