14691297

pubmed:Citation

12

Central nervous system dysfunction is commonly observed in children with HIV-1 infection, but the mechanisms whereby HIV-1 causes encephalopathy are not completely understood. We have previously shown that human brain microvascular endothelial cells (HBMEC) from children are responsive to gp120 derived from X4 HIV-1 by increasing expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule-1. However, the mechanisms involved in gp120-mediated up-regulation of cell adhesion molecule expression is unclear. In the present study, we found that gp120 derived from both X4 and R5 HIV-1 induced increased expression of ICAM-1 on HBMEC, but the degree of this up-regulation differed among the various HBMEC isolates. The up-regulation of ICAM-1 was inhibited by anti-CD4 antibodies as well as by specific antibodies directed against chemokine receptors and small-molecule coreceptor inhibitors. Anti-CD4 antibodies inhibited the increase in ICAM-1 expression mediated by gp120 derived from X4 and R5 HIV-1, whereas antibodies against chemokine receptors displayed a differential inhibition depending on the source of gp120. Both X4 and R5 gp120-induced ICAM-1 expression was sensitive to pertussis toxin and involved the nuclear factor-kB pathway. These findings indicate a direct involvement of CD4 and a differential involvement of chemokine receptors in the activation of pediatric HBMEC by X4 and R5 gp120. The activation of brain endothelium of children by HIV-1 protein gp120 by way of CD4 and chemokine receptors may have implications for the pathogenesis of HIV-1 encephalopathy in the pediatric population.

eng

IM

MEDLINE

0023-6837

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NLM

1787-98

pubmed-meshheading:14691297-Antibodies, Blocking, pubmed-meshheading:14691297-Antigens, CD4, pubmed-meshheading:14691297-Cells, Cultured, pubmed-meshheading:14691297-Child, pubmed-meshheading:14691297-Endothelium, Vascular, pubmed-meshheading:14691297-HIV Envelope Protein gp120, pubmed-meshheading:14691297-HIV-1, pubmed-meshheading:14691297-Humans, pubmed-meshheading:14691297-Intercellular Adhesion Molecule-1, pubmed-meshheading:14691297-Microcirculation, pubmed-meshheading:14691297-NF-kappa B, pubmed-meshheading:14691297-Nitriles, pubmed-meshheading:14691297-Organic Chemicals, pubmed-meshheading:14691297-Pertussis Toxin, pubmed-meshheading:14691297-RNA, Messenger, pubmed-meshheading:14691297-Receptors, CXCR4, pubmed-meshheading:14691297-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:14691297-Sulfones

Induction of intercellular adhesion molecule-1 on human brain endothelial cells by HIV-1 gp120: role of CD4 and chemokine coreceptors.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't