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Interactions between macrophages and brain microvascular endothelial cells: role in pathogenesis of HIV-1 infection
1Eijkman-Winkler Institute of Microbiology, Infectious Diseases and Inflammation, section of Neuroimmunology, Utrecht University, Utrecht, The Netherlands.
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.
Insights
Preventing monocyte infiltration into the brain is key for treating neurological disorders like AIDS dementia complex. Understanding monocyte-endothelial cell interactions at the blood-brain barrier is crucial for developing new therapies.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Monocyte infiltration into brain tissue is implicated in neurological disorders, leading to neuronal damage.
- Activated macrophages in the brain contribute to functional loss and reduced neuronal viability.
Purpose of the Study:
- To elucidate the cellular mechanisms of monocyte infiltration across the blood-brain barrier in HIV-1 infection.
- To identify therapeutic targets for preventing monocyte entry into the central nervous system.
Main Methods:
- Investigated the roles of E-selectin and vascular cell adhesion molecule-1 in monocyte adhesion to endothelial cells.
- Examined the contribution of nitric oxide and gelatinase B to monocyte transmigration.
- Analyzed the role of chemokines in regulating monocyte traffic within the brain parenchyma.
Main Results:
- Monocytes adhere to endothelial cells via E-selectin and vascular cell adhesion molecule-1.
- Nitric oxide and gelatinase B facilitate monocyte transmigration across the blood-brain barrier.
- Chemokines produced by brain endothelial cells and within the brain promote monocyte influx and traffic.
Conclusions:
- Brain microvascular endothelial cells play a significant role in the neuropathogenesis of HIV-1 infection.
- Targeting monocyte adhesion and transmigration mechanisms offers potential therapeutic strategies.
- Understanding these interactions is vital for developing treatments for HIV-associated neurological disorders.