title: HIV infection of macrophages is enhanced in the presence of increased expression of CD163 induced by substance P.
abstract: Activation of NK1R by SP contributes to increased HIV-1 infection in macrophages. The scavenger receptor CD163 is expressed on cells of monocyte-macrophage origin. Our main goal was to determine if there is interplay among SP, CD163 expression, and HIV infection in macrophages. We showed that SP triggers intracellular calcium elevation and increased CD163 expression in human monocytes in a time- and concentration-dependent manner. The role of CD163 on HIV infection was examined by RT-PCR in sorted monocytes (CD163(low) and CD163(high)) and in macrophages having CD163 knocked down using siRNA. We found that the productivity of HIV infection was higher in CD163(high) cells. Additionally, in macrophages with CD163 expression knocked down, we found a significant decrease of HIV infection. Furthermore, Hb-Hp complexes, which function as an endogenous ligand for CD163, decreased HIV infection in macrophages in a dose-dependent manner. Thus, we demonstrate that SP induces higher levels of CD163 in monocytes and that high expression of CD163 is associated with increases HIV infection in macrophages. Thus, in addition to being a prognostic marker of HIV infection, the expression of CD163 on macrophages may be critical in HIV immunopathogenesis.
authors.affiliation: Division of Allergy and Immunology and Flow Cytometry Core Laboratory, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, USA; and Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA tuluc@email.chop.edu.
authors.forename: Florin
authors.initials: F
authors.lastname: Tuluc
authors.affiliation: Division of Allergy and Immunology and.
authors.forename: John
authors.initials: J
authors.lastname: Meshki
authors.affiliation: Division of Allergy and Immunology and.
authors.forename: Sergei
authors.initials: S
authors.lastname: Spitsin
authors.affiliation: Division of Allergy and Immunology and Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis* / Q000276:immunology; D015415:Biomarkers; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000276:immunology; D013373:Substance P / Q000494:pharmacology*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D018377:Neurotransmitter Agents; D011956:Receptors, Cell Surface; D013373:Substance P
keywords: AIDS; haptoglobin; hemoglobin; monocytes; neurocognitive impairment