Altered regulation of CD200 receptor in monocyte-derived macrophages from individuals with Parkinson's disease.
Microglia are the representative myeloid cells in the brain, and their over-activation plays an important role in the pathogenesis of Parkinson's disease (PD). Microglia activation is believed to be regulated by the CD200-CD200R signaling. As the peripheral counterpart of microglia, monocyte-derived macrophages (MDMs) share the same progenitor and antigen markers, and they have similar biological behaviors and mirror microglial function in the brain. Here, we studied CD200R expression and its regulation in MDMs from 32 PD cases, 27 age-matched old controls, and 28 young controls. We found that the basal CD200R expression is similar in MDMs from young control, old control and PD patients. However, the induction of CD200R expression in MDMs under various conditions is impaired in the old groups, especially in PD patients. There was a selective decrease in CD200R expression induced by co-culture with dying PC12 cells in MDMs from PD cases, as compared with MDMs from the age-matched controls. We also found that the inducible CD200R expression correlated inversely with the onset age of PD and to tumor necrosis factor-alpha (TNF-alpha) released from MDMs. These results suggest an intrinsic abnormality in the CD200-CD200R signaling in MDMs during aging and, especially, in PD. We speculate that in the PD brain,microglia might undergo abnormalities similar to MDMs.
Luo
Xiao-Guang
XG
Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Jiaotong Univeristy School of Medicine, Shanghai, Luwan District, China. chunlinge@yahoo.com.cn
Zhang
Ji-Juan
JJ
Zhang
Chao-Dong
CD
Liu
Rong
R
Zheng
Lan
L
Wang
Xi-Jin
XJ
Chen
Sheng-Di
SD
Ding
Jian-Qing
JQ
D015703:Antigens, CD / Q000378:metabolism*; D016022:Case-Control Studies; D017077:Culture Media, Conditioned; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D017077:Culture Media, Conditioned; D014409:Tumor Necrosis Factor-alpha; C042739:antigens, CD200