Interactions between macrophages and brain microvascular endothelial cells: role in pathogenesis of HIV-1 infection and blood - brain barrier function.

Abstract

Monocytes have been shown to infiltrate in brain tissue during various neurological disorders including AIDS dementia complex. The presence of an excess of activated macrophages in brain tissue is accompanied by tissue damage resulting in a loss in neuronal function and viability. Therapeutic options against such neurological disorders could therefore be aimed at the prevention of monocyte infiltration across the blood - brain barrier. Therefore, a better understanding of these processes is needed. Recent insights in cellular processes between monocytes/macrophages and brain microvascular endothelial cells in the neuropathogenesis of HIV-1 infection demonstrate that monocytes roll on endothelial cells via the inducible endothelial adhesion molecule E-selectin. Binding of these cells are mainly mediated via the endothelial adhesion molecule vascular cell adhesion molecule-1. The transmigration through the blood - brain barrier is facilitated by both endothelial and monocyte/macrophage-derived nitric oxide and by the increased production of gelatinase B activity by HIV-infected monocytes/macrophages. Chemokines produced within the brain regulate the traffic of the infiltrating monocytes through the brain parenchyma. In addition, endothelial cells also produce monocyte attracting chemokines during their first interactions with HIV-infected monocytes/macrophages thus promoting additional influx of phagocytes into the brain. Furthermore, excessive infiltration of monocytes is accompanied by endothelial damage resulting in the loss of tight junctions. Thus, in toto, brain microvascular endothelial cells might contribute to the neuropathogenesis of HIV-1 infection.

• Authors: H S Nottet
• Journal: Journal of neurovirology (J Neurovirol) Vol. 5 Issue 6 Pg. 659-69 (Dec 1999) ISSN: 1355-0284 [Print] United States
• PMID: 10602406 (Publication Type: Journal Article, Review)

Chemical References

• Anti-HIV Agents
• Anti-Inflammatory Agents
• E-Selectin
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Matrix Metalloproteinase 9

Topics

• AIDS Dementia Complex (drug therapy, physiopathology)
• Animals
• Anti-HIV Agents (therapeutic use)
• Anti-Inflammatory Agents (therapeutic use)
• Blood-Brain Barrier (drug effects, physiology)
• Brain (blood supply, cytology, virology)
• Cell Adhesion
• Cell Movement
• E-Selectin (metabolism)
• Endothelium, Vascular (cytology, metabolism)
• HIV Infections (virology)
• HIV-1 (pathogenicity)
• Humans
• Intercellular Adhesion Molecule-1 (metabolism)
• Macrophages (metabolism, virology)
• Matrix Metalloproteinase 9 (metabolism)
• Monocytes (metabolism, virology)
• Vascular Cell Adhesion Molecule-1 (metabolism)