Fractalkine (CX3CL1) and brain inflammation: Implications for HIV-1-associated dementia.
Leukocyte migration and activation play an important role in immune surveillance and the pathogenesis of a variety of neurodegenerative disorders, including human immunodeficiency virus (HIV)-1-associated dementia (HAD). A novel chemokine named fractalkine (FKN, CX3CL1), which exists in both membrane-anchored and soluble isoforms, has been proposed to participate in the generation and progression of inflammatory brain disorders. Upon binding to the CX3C receptor one (CX3CR1), FKN induces adhesion, chemoattraction, and activation of leukocytes, including brain macrophages and microglia (MP). Constitutively expressed in the central nervous system (CNS), mainly by neurons, FKN is up-regulated and released in response to proinflammatory stimuli. Importantly, FKN is up-regulated in the brain tissue and cerebrospinal fluid (CSF) of HAD patients. Together, these observations suggest that FKN and its receptor have a unique role in regulating the neuroinflammatory events underlying disease. This review will examine how FKN contributes to the recruitment and activation of CX3CR1-expressing MP, which are critical events in the neuropathogenesis of HAD.
Cotter
R
R
The Laboratory of Neurotoxicology, the Center for Neurovirology and Neurodegenerative Disorders, Department of Pathology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Williams
C
C
Ryan
L
L
Erichsen
David
D
Lopez
A
A
Peng
H
H
Zheng
J
J
D015526:AIDS Dementia Complex / Q000276:immunology*; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000276:immunology*; D004660:Encephalitis / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*
C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins