Role of Fcgamma receptors in nigral cell injury induced by Parkinson disease immunoglobulin injection into mouse substantia nigra.
Immune/inflammatory factors have been implicated in the pathogenesis of Parkinson's disease (PD). Immunoglobulin G (IgG) from patients with PD can induce injury of dopaminergic neurons following stereotaxic injection into rat substantia nigra (SN). The PD IgG can be demonstrated in vitro to activate microglia via the Fcgamma receptor (Fcgamma R) and induce dopaminergic cell injury. To confirm the involvement of microglia and their Fcgamma R in IgG-induced lesions of SN in vivo we analyzed the tyrosine hydroxylase (TH)-positive cell loss in SN par compacta (SNpc) in mice lacking Fcgamma receptors (Fcgamma R(-/-)) and wild type (Fcgamma R(+/+)). At 1 day after stereotaxic injection of PD IgG into the SN of Fcgamma R(+/+) mice there was a 27% increase in the number of CD11b-positive microglial cells and no significant loss of TH-positive cells. At 14 days after the stereotaxic injection, the number of microglial cells was increased by 42%, accompanied by a 40% loss of TH-positive neurons in the SNpc. PD IgG injection in Fcgamma R(-/-) mice resulted in no significant increase of microglia and no loss of TH-positive cells in the SNpc at any time point. The injection of F(ab')(2) fragments of PD IgG was able to induce TH-positive neuronal loss in the SNpc only when the injected animals raised antibodies against the injected human IgG fragments, which confirmed the importance of the Fcgamma R in microglial activation and nigral injury.
D000818:Animals; D000906:Antibodies / Q000097:blood; D002452:Cell Count; D006720:Homozygote; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000494:pharmacology; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008845:Microinjections; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010300:Parkinson Disease / Q000276:immunology*; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013238:Stereotaxic Techniques; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
D000906:Antibodies; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D016177:Macrophage-1 Antigen; D017452:Receptors, IgG; D014446:Tyrosine 3-Monooxygenase