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

Dionna W. Williams, Kathryn Anastos, Susan Morgello, Joan W. Berman

Research output: Contribution to journalArticle

37 Scopus citations

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 HIVpositive 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 CD14lowCD16+ monocytes was increased in HIVseropositive 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.

Original languageEnglish (US)
Pages (from-to)401-412
Number of pages12
JournalJournal of Leukocyte Biology
Volume97
Issue number2
DOIs
StatePublished - Feb 1 2015

Keywords

  • AIDS
  • Junctional proteins
  • Transmigration

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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