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.
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.
Vinet-Oliphant
Heather
H
Tulane National Primate Research Center, Division of Comparative Pathology, Covington, LA 70433, USA.
Alvarez
Xavier
X
Buza
Elizabeth
E
Borda
Juan T
JT
Mohan
Mahesh
M
Aye
Pyone P
PP
Tuluc
Florin
F
Douglas
Steven D
SD
Lackner
Andrew A
AA
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*
D018040:Receptors, Neurokinin-1; D013373:Substance P