JAM-A and ALCAM are therapeutic targets to inhibit diapedesis across the BBB of CD14+CD16+ monocytes in HIV-infected individuals.
Title | JAM-A and ALCAM are therapeutic targets to inhibit diapedesis across the BBB of CD14+CD16+ monocytes in HIV-infected individuals. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Williams, DW, Anastos, K, Morgello, S, Berman, JW |
Journal | J Leukoc Biol |
Volume | 97 |
Issue | 2 |
Pagination | 401-12 |
Date Published | 2015 Feb |
ISSN | 1938-3673 |
Keywords | Adult, Antigens, CD, Blood-Brain Barrier, Cell Adhesion Molecules, Cell Adhesion Molecules, Neuronal, Cohort Studies, Female, Fetal Proteins, Gene Expression Regulation, GPI-Linked Proteins, HIV Infections, Humans, Inflammation, Internal, Lipopolysaccharide Receptors, 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. |
URL | https://www.ncbi.nlm.nih.gov/pubmed/25420915 |
DOI | 10.1189/jlb.5A0714-347R |
Alternate Journal | J Leukoc Biol |
PubMed ID | 25420915 |
PubMed Central ID | PMC4304417 |
Grant List | R01 DA025567 / DA / NIDA NIH HHS / United States U24 MH100929 / MH / NIMH NIH HHS / United States U01 MH083500 / MH / NIMH NIH HHS / United States U24 MH100931 / MH / NIMH NIH HHS / United States AI142590 / AI / NIAID NIH HHS / United States MH090958 / MH / NIMH NIH HHS / United States U01 AI035004 / AI / NIAID NIH HHS / United States AI051519 / AI / NIAID NIH HHS / United States P30 AI051519 / AI / NIAID NIH HHS / United States MH083501 / MH / NIMH NIH HHS / United States DA025567 / DA / NIDA NIH HHS / United States AI035004 / AI / NIAID NIH HHS / United States R25 MH080663 / MH / NIMH NIH HHS / United States MH080663 / MH / NIMH NIH HHS / United States MH075679 / MH / NIMH NIH HHS / United States MH100931 / MH / NIMH NIH HHS / United States U01 MH083501 / MH / NIMH NIH HHS / United States R01 MH090958 / MH / NIMH NIH HHS / United States T32 AI070117 / AI / NIAID NIH HHS / United States R01 MH075679 / MH / NIMH NIH HHS / United States AI070117 / AI / NIAID NIH HHS / United States |