title: 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.
abstract: 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.affiliation: Tulane National Primate Research Center, Division of Comparative Pathology, Covington, LA 70433, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Vinet-Oliphant
authors.forename: Xavier
authors.initials: X
authors.lastname: Alvarez
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Buza
authors.forename: Juan T
authors.initials: JT
authors.lastname: Borda
authors.forename: Mahesh
authors.initials: M
authors.lastname: Mohan
authors.forename: Pyone P
authors.initials: PP
authors.lastname: Aye
authors.forename: Florin
authors.initials: F
authors.lastname: Tuluc
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Lackner
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D002465:Cell Movement; D002478:Cells, Cultured; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008253:Macaca mulatta; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018613:Microscopy, Confocal; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018040:Receptors, Neurokinin-1 / Q000276:immunology / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013373:Substance P / Q000276:immunology / Q000378:metabolism*
chemical_list: D018040:Receptors, Neurokinin-1; D013373:Substance P