The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis.
Macrophage/microglia (M phi) are the principal immune cells in the central nervous system (CNS) concomitant with inflammatory brain disease and play a significant role in the host defense against invading microorganisms. Astrocytes, as a significant component of the blood-brain barrier, behave as one of the immune effector cells in the CNS as well. However, both cell types may play a dual role, amplifying the effects of inflammation and mediating cellular damage as well as protecting the CNS. Interactions of the immune system, M phi, and astrocytes result in altered production of neurotoxins and neurotrophins by these cells. These effects alter the neuronal structure and function during pathogenesis of HIV-1-associated dementia (HAD), Alzheimer disease (AD), and multiple sclerosis (MS). HAD primarily involves subcortical gray matter, and both HAD and MS affect sub-cortical white matter. AD is a cortical disease. The process of M phi and astrocytes activation leading to neurotoxicity share similarities among the three diseases. Human Immunodeficiency Virus (HIV)-1-infected M phi are involved in the pathogenesis of HAD and produce toxic molecules including cytokines, chemokines, and nitric oxide (NO). In AD, M phis produce these molecules and are activated by beta-amyloid proteins and related oligopeptides. Demyelination in MS involves M phi that become lipid laden, spurred by several possible antigens. In these three diseases, cytokine/chemokine communications between M phi and astrocytes occur and are involved in the balance of protective and destructive actions by these cells. This review describes the role of M phi and astrocytes in the pathogenesis of these three progressive neurological diseases, examining both beneficent and deleterious effects in each disease.
Minagar
Alireza
A
Department of Neurology, Louisiana State University School of Medicine, Shreveport, LA 71130, USA. aminag@lsuhsc.edu
Shapshak
Paul
P
Fujimura
Robert
R
Ownby
Ray
R
Heyes
Melvin
M
Eisdorfer
Carl
C
D015526:AIDS Dementia Complex / Q000209:etiology / Q000276:immunology*; D000544:Alzheimer Disease / Q000209:etiology / Q000276:immunology*; D017951:Antigen Presentation; D001253:Astrocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D017628:Microglia / Q000276:immunology*; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology*