Mononuclear phagocytes mediate blood-brain barrier compromise and neuronal injury during HIV-1-associated dementia. 2000

Y Persidsky, and J Zheng, and D Miller, and H E Gendelman
Center for Neurovirology and Neurodegenerative Disorders, the Department of Pathology, University of Nebraska Medical Center, Omaha 68198-5215, USA. ypersids@unmc.edu

The neuropathogenesis of HIV-1 infection revolves around the production of secretory factors from immune-activated brain mononuclear phagocytes (MP). MP-secreted chemokines may play several roles in HIV-1 encephalitis (HIVE). These can promote macrophage brain infiltration, blood-brain barrier (BBB) and neuronal dysfunction during HIV-1-associated dementia. We investigate how HIV-1-infected MP regulates the production of chemokines and how they influence HIV-1 neuropathogenesis. We demonstrate that HIV-1-infected and immune-activated MP (for example, microglia) and astrocytes produce beta-chemokines in abundance, as shown in both laboratory assays and within infected brain tissue. HIV-1-infected microglia significantly modulate monocyte migration in a BBB model system and in brains of SCID mice with HIVE. HIV-1-infected MP down-regulate tight junction protein and special polarized transport systems on brain microvascular endothelial cells as shown in human autopsy brain tissue and in SCID mice with HIVE. Chemokines can damage neurons directly. Toxicity caused by binding of stromal-derived factor-1alpha to its receptor on neurons exemplifies such mechanism. In toto, these works underscore the diverse roles of chemokines in HIV-1 neuropathogenesis and lay the foundation for future therapeutic interventions.

UI MeSH Term Description Entries
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010586 Phagocytes Cells that can carry out the process of PHAGOCYTOSIS. Phagocyte,Phagocytic Cell,Phagocytic Cells,Cell, Phagocytic,Cells, Phagocytic
D001812 Blood-Brain Barrier Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue. Brain-Blood Barrier,Hemato-Encephalic Barrier,Barrier, Blood-Brain,Barrier, Brain-Blood,Barrier, Hemato-Encephalic,Barriers, Blood-Brain,Barriers, Brain-Blood,Barriers, Hemato-Encephalic,Blood Brain Barrier,Blood-Brain Barriers,Brain Blood Barrier,Brain-Blood Barriers,Hemato Encephalic Barrier,Hemato-Encephalic Barriers
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001253 Astrocytes A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury. Astroglia,Astroglia Cells,Astroglial Cells,Astrocyte,Astroglia Cell,Astroglial Cell,Astroglias,Cell, Astroglia,Cell, Astroglial
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015526 AIDS Dementia Complex A neurologic condition associated with the ACQUIRED IMMUNODEFICIENCY SYNDROME and characterized by impaired concentration and memory, slowness of hand movements, ATAXIA, incontinence, apathy, and gait difficulties associated with HIV-1 viral infection of the central nervous system. Pathologic examination of the brain reveals white matter rarefaction, perivascular infiltrates of lymphocytes, foamy macrophages, and multinucleated giant cells. (From Adams et al., Principles of Neurology, 6th ed, pp760-1; N Engl J Med, 1995 Apr 6;332(14):934-40) AIDS Encephalopathy,Dementia Complex, AIDS-Related,HIV Dementia,HIV Encephalopathy,HIV-1-Associated Cognitive Motor Complex,HIV-Associated Cognitive Motor Complex,AIDS-Related Dementia Complex,Acquired-Immune Deficiency Syndrome Dementia Complex,Dementia Complex, Acquired Immune Deficiency Syndrome,Encephalopathy, AIDS,Encephalopathy, HIV,HIV-1 Cognitive and Motor Complex,AIDS Encephalopathies,AIDS Related Dementia Complex,Complex, AIDS Dementia,Complex, AIDS-Related Dementia,Dementia Complex, AIDS,Dementia Complex, AIDS Related,Dementia, HIV,Dementias, HIV,Encephalopathies, AIDS,Encephalopathies, HIV,HIV 1 Associated Cognitive Motor Complex,HIV 1 Cognitive and Motor Complex,HIV Associated Cognitive Motor Complex,HIV Dementias,HIV Encephalopathies
D017628 Microglia The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. Microglial Cell,Cell, Microglial,Microglial Cells,Microglias

Related Publications

Y Persidsky, and J Zheng, and D Miller, and H E Gendelman
December 2016, Neurology(R) neuroimmunology & neuroinflammation,
Y Persidsky, and J Zheng, and D Miller, and H E Gendelman
March 2002, Cellular and molecular biology (Noisy-le-Grand, France),
Y Persidsky, and J Zheng, and D Miller, and H E Gendelman
October 2002, Journal of acquired immune deficiency syndromes (1999),
Y Persidsky, and J Zheng, and D Miller, and H E Gendelman
May 2003, Journal of neuroimmunology,
Y Persidsky, and J Zheng, and D Miller, and H E Gendelman
July 2006, Current HIV research,
Y Persidsky, and J Zheng, and D Miller, and H E Gendelman
December 2002, Alcoholism, clinical and experimental research,
Y Persidsky, and J Zheng, and D Miller, and H E Gendelman
August 1997, Current opinion in neurology,
Y Persidsky, and J Zheng, and D Miller, and H E Gendelman
October 1994, Journal of virology,
Y Persidsky, and J Zheng, and D Miller, and H E Gendelman
November 1994, Journal of leukocyte biology,
Y Persidsky, and J Zheng, and D Miller, and H E Gendelman
January 1994, Gematologiia i transfuziologiia,
Copied contents to your clipboard!