Importance of macrophage inflammatory protein-1α and splenic macrophages in neurodegeneration induced by PVC-211 murine leukemia virus.
We recently reported that infection of rats with the neurodegenerative disease-causing retrovirus PVC-211 MuLV results in elevated levels of the chemokine MIP-1α followed by the accumulation of activated microglia in the brain. To investigate the importance of MIP-1α in recruitment of microglia to the brain, we treated rats with MIP-1α antibodies before and after PVC-211 MuLV infection. This caused a delay in the development of paralysis which was associated with a decrease in activated microglia without affecting virus expression. To determine the source of activated microglia, rats were splenectomized 4 days after virus infection. Splenectomized rats showed a delay in disease development that was associated with decreased numbers of activated microglia without affecting virus expression. Together, these results suggest that MIP-1α is directly involved in the neurodegeneration induced in rats by PVC-211 MuLV by recruiting macrophages/microglia from the periphery into regions of the brain that eventually become diseased.
Laboratory of Cancer Prevention, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
Xiujie
X
Li
Xiang
X
Zhang
Joan L
JL
Cmarik
Sandra
S
Ruscetti
D000818:Animals; D009052:Leukemia Virus, Murine / Q000276:immunology / Q000472:pathogenicity*; D019402:Macrophage Inflammatory Proteins / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D017628:Microglia / Q000276:immunology / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000276:immunology / Q000473:pathology* / Q000821:virology; D010243:Paralysis / Q000473:pathology / Q000821:virology; D051381:Rats; D012192:Retroviridae Infections / Q000276:immunology / Q000473:pathology* / Q000821:virology
D019402:Macrophage Inflammatory Proteins