title: JAM-A and ALCAM are therapeutic targets to inhibit diapedesis across the BBB of CD14+CD16+ monocytes in HIV-infected individuals.
abstract: Monocyte transmigration across the BBB is a critical step in the development of cognitive deficits termed HAND that affect 40-70% of HIV-infected individuals, even with successful antiretroviral therapy. The monocyte subsets that enter the CNS during HIV infection are not fully characterized. We examined PBMC from HIV-positive individuals from 2 distinct cohorts and enumerated monocyte populations, characterized their transmigration properties across an in vitro human BBB model, and identified surface proteins critical for the entry of these cells into the CNS. We demonstrated that the frequency of peripheral blood CD14(+)CD16(+) and CD14(low)CD16(+) monocytes was increased in HIV-seropositive compared with -seronegative individuals, despite virologic control. We showed that CD14(+)CD16(+) monocytes selectively transmigrated across our BBB model as a result of their increased JAM-A and ALCAM expression. Antibody blocking of these proteins inhibited diapedesis of CD14(+)CD16(+) monocytes but not of T cells from the same HIV-infected people across the BBB. Our data indicate that JAM-A and ALCAM are therapeutic targets to decrease the entry of CD14(+)CD16(+) monocytes into the CNS of HIV-seropositive individuals, contributing to the eradication of neuroinflammation, HAND, and CNS viral reservoirs.
authors.affiliation: Departments of *Pathology, Medicine and Epidemiology and Population Health, and Microbiology and Immunology, The Albert Einstein College of Medicine, Bronx, New York, USA; and Departments of Neurology, Neuroscience, and Pathology, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Dionna W
authors.initials: DW
authors.lastname: Williams
authors.affiliation: Departments of *Pathology, Medicine and Epidemiology and Population Health, and Microbiology and Immunology, The Albert Einstein College of Medicine, Bronx, New York, USA; and Departments of Neurology, Neuroscience, and Pathology, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.affiliation: Departments of *Pathology, Medicine and Epidemiology and Population Health, and Microbiology and Immunology, The Albert Einstein College of Medicine, Bronx, New York, USA; and Departments of Neurology, Neuroscience, and Pathology, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.affiliation: Departments of *Pathology, Medicine and Epidemiology and Population Health, and Microbiology and Immunology, The Albert Einstein College of Medicine, Bronx, New York, USA; and Departments of Neurology, Neuroscience, and Pathology, The Icahn School of Medicine at Mount Sinai, New York, New York, USA joan.berman@einstein.yu.edu.
authors.forename: Joan W
authors.initials: JW
authors.lastname: Berman
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology*; D001812:Blood-Brain Barrier / Q000276:immunology* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D015816:Cell Adhesion Molecules, Neuronal / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D005326:Fetal Proteins / Q000276:immunology*; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D018950:Lipopolysaccharide Receptors; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D017452:Receptors, IgG; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology*; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C407243:F11R protein, human; C428200:FCGR3B protein, human
keywords: AIDS; junctional proteins; transmigration