JAM-A and ALCAM are therapeutic targets to inhibit diapedesis across the BBB of CD14+CD16+ monocytes in HIV-infected individuals.

TitleJAM-A and ALCAM are therapeutic targets to inhibit diapedesis across the BBB of CD14+CD16+ monocytes in HIV-infected individuals.
Publication TypeJournal Article
Year of Publication2015
AuthorsWilliams, DW, Anastos, K, Morgello, S, Berman, JW
JournalJ Leukoc Biol
Volume97
Issue2
Pagination401-12
Date Published2015 Feb
ISSN1938-3673
KeywordsAdult, Antigens, CD, Antigens, CD14, Blood-Brain Barrier, Cell Adhesion Molecules, Cell Adhesion Molecules, Neuronal, Cohort Studies, External, Female, Fetal Proteins, Gene Expression Regulation, GPI-Linked Proteins, HIV Infections, Humans, Inflammation, Male, Middle Aged, Monocytes, Receptors, Cell Surface, Receptors, IgG, Transendothelial and Transepithelial Migration
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.

DOI10.1189/jlb.5A0714-347R
Alternate JournalJ. Leukoc. Biol.
PubMed ID25420915
PubMed Central IDPMC4304417
Grant ListAI035004 / AI / NIAID NIH HHS / United States
AI051519 / AI / NIAID NIH HHS / United States
AI070117 / AI / NIAID NIH HHS / United States
AI142590 / AI / NIAID NIH HHS / United States
DA025567 / DA / NIDA NIH HHS / United States
MH075679 / MH / NIMH NIH HHS / United States
MH080663 / MH / NIMH NIH HHS / United States
MH083501 / MH / NIMH NIH HHS / United States
MH090958 / MH / NIMH NIH HHS / United States
MH100931 / MH / NIMH NIH HHS / United States
R25 MH080663 / MH / NIMH NIH HHS / United States
U01 AI035004 / AI / NIAID NIH HHS / United States
U24 MH100931 / MH / NIMH NIH HHS / United States