title: Characterization of monocyte maturation/differentiation that facilitates their transmigration across the blood-brain barrier and infection by HIV: implications for NeuroAIDS.
abstract: The prevalence of human immunodeficiency virus 1 (HIV) associated neurocognitive disorders resulting from infection of the central nervous system (CNS) by HIV continues to increase despite the success of combination antiretroviral therapy. Although monocytes are known to transport HIV across the blood-brain barrier (BBB) into the CNS, there are few specific markers that identify monocyte subpopulations susceptible to HIV infection and/or capable of infiltrating the CNS. We cultured human peripheral blood monocytes and characterized the expression of the phenotypic markers CD14, CD16, CD11b, Mac387, CD163, CD44v6 and CD166 during monocyte/macrophage (Mo/Mac) maturation/differentiation. We determined that a CD14(+)CD16(+)CD11b(+)Mac387(+) Mo/Mac subpopulation preferentially transmigrates across our in vitro BBB model in response to CCL2. Genes associated with Mo/Mac subpopulations that transmigrate across the BBB and/or are infected by HIV were identified by cDNA microarray analyses. Our findings contribute to the understanding of monocyte maturation, infection and transmigration into the brain during the pathogenesis of NeuroAIDS.
authors.affiliation: Departments of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Clarisa M
authors.initials: CM
authors.lastname: Buckner
authors.forename: Tina M
authors.initials: TM
authors.lastname: Calderon
authors.forename: Dionna W
authors.initials: DW
authors.lastname: Willams
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Belbin
authors.forename: Joan W
authors.initials: JW
authors.lastname: Berman
mesh_terms: D015526:AIDS Dementia Complex / Q000209:etiology*; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology; D001812:Blood-Brain Barrier / Q000166:cytology*; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002469:Cell Separation / Q000379:methods; D018932:Chemokine CCL2 / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology; D058851:GPI-Linked Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D006678:HIV; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D039942:Neuropilin-1 / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D054390:Receptors, CCR2 / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; C515334:CCR2 protein, human; D039481:CD11b Antigen; D018932:Chemokine CCL2; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D054390:Receptors, CCR2; D017452:Receptors, IgG; D039942:Neuropilin-1; D016173:Macrophage Colony-Stimulating Factor; D010751:Phosphopyruvate Hydratase