Identification of FcγRI, II and III on normal human brain ramified microglia and on microglia in senile plaques in Alzheimer's disease

Peress, Nancy S.; Fleit, Howard B.; Perillo, Edward; Kuljiš, Rodrigo O.; C, Pezzullo

doi:10.1016/0165-5728(93)90060-c

Cited by 98 publications

(66 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Microglia was found to make up 7.5 -9% of the total glial population in white matter (Akiyama and Mc Geer, 1990). These cells have a leucocyte origin (Flugel et al, 2001), phagocytic function and can produce a cytotoxic action when triggered by antibody coated through Fc gamma receptors (Peress et al, 1993;Vedeler et al, 1994). Proteins (150 kDa) such as IgG are supposed to cross the abnormal GBM blood -brain barrier (Vajkoczy et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Recombinant humanised anti-HER2/neu antibody (Herceptin®) induces cellular death of glioblastomas

et al. 2004

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) remains the most devastating primary tumour in neuro-oncology. Targeting of the human epithelial receptor type 2 (HER2)-neu receptor by specific antibodies is a recent well-established therapy for breast tumours. Human epithelial receptor type 2/neu is a transmembrane tyrosine/kinase receptor that appears to be important for the regulation of cancer growth. Human epithelial receptor type 2/neu is not expressed in the adult central nervous system, but its expression increases with the degree of astrocytoma anaplasia. The specificity of HER2/neu for tumoral astrocytomas leads us to study in vitro treatment of GBM with anti-HER2/neu antibody. We used human GBM cell lines expressing HER2/neu (A172 express HER2/neu more than U251MG) or not (U87MG) and monoclonal humanised antibody against HER2/neu (Herceptin s ). Human epithelial receptor type 2/neu expression was measured by immunohistochemistry and flow cytometry. Direct antibody effect, complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity were evaluated by different cytometric assays. We have shown, for the first time, the ability of anti-HER2/neu antibodies to induce apoptosis and cellular-dependent cytotoxicity of HER2/neu-expressing GBM cell lines. The results decreased from A172 to U251 and were negative for U87MG, in accordance with the decreasing density of HER2/neu receptors.

show abstract

Section: Discussionmentioning

confidence: 99%

Recombinant humanised anti-HER2/neu antibody (Herceptin®) induces cellular death of glioblastomas

et al. 2004

View full text Add to dashboard Cite

show abstract

“…AD has a significant inflammatory component evidenced by abundant plaque-associated microglia that exhibit a reactive phenotype (Akiyama and McGeer, 1990;Masliah et al, 1991;Peress et al, 1993;Akiyama et al, 2000). The activated microglia release a diverse array of proinflammatory molecules that act to exacerbate the disease process and contribute to neuronal death (Combs et al, 2000(Combs et al, , 2001bYates et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors Attenuate β-Amyloid-Induced Microglial Inflammatory Responses

Cordle¹,

Landreth²

2005

J. Neurosci.

161

109

View full text Add to dashboard Cite

Alzheimer's disease (AD) is characterized by extracellular deposits of fibrillar ␤-amyloid (A␤) in the brain, a fulminant microglialmediated inflammatory reaction, and neuronal death. The use of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) is associated with a reduced risk of AD, which has been attributed to the cholesterol-lowering actions of these drugs. Statins have been reported recently to have anti-inflammatory actions in addition to their classic lipid-lowering effects. We report that statins robustly inhibited the A␤-stimulated expression of interleukin-1␤ and inducible nitric oxide synthase and the production of nitric oxide by microglia and monocytes. Statin treatment also blocked the rac1-dependent activation of NADPH oxidase and superoxide production. The anti-inflammatory actions of the statins were attributable to their ability to reduce the levels of isoprenyl intermediates in the cholesterol biosynthetic pathway. The effect of statins could not be reversed by exogenous cholesterol supplementation, indicating that the anti-inflammatory actions are distinct from their cholesterol-lowering actions. The addition of the isoprenyl precursors, mevalonic acid, and geranylgeranyl pyrophosphate (GGpp) attenuated the statin-mediated downregulation of inflammatory markers. Prevention of protein isoprenylation by the GGpp transferase inhibitor (GGTI-286) or inhibition of Rho-family function with Clostridium difficile Toxin A blocked the inflammatory response similar to the effect of statin treatment. We argue that the statin-mediated decrease in AD risk arises from their pleiotropic actions, effecting a reduction in neuronal A␤ production and microglia-directed inflammation.

show abstract

“…Although IgG is absent or extremely low-level in the CNS, FcγRs also accumulate in the plaques and microglial cells of AD brains (18). Further, one immune inhibitory receptor, CD33, was isolated as an AD risk factor in genome-wide association studies (GWAS) (45).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it was reported that FcγRIIb is also expressed in Purkinje cells and regulates cerebellar functions in the brain (17). Although there are a growing number of reports showing the expression and function of IgG-binding Fcγ receptors (FcγRs) in the CNS (18,19), the neuronal function of FcγRIIb in the brain is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

FcγRIIb mediates amyloid-β neurotoxicity and memory impairment in Alzheimer’s disease

et al. 2013

View full text Add to dashboard Cite

Amyloid-β (Aβ) induces neuronal loss and cognitive deficits and is believed to be a prominent cause of Alzheimer's disease (AD); however, the cellular pathology of the disease is not fully understood. Here, we report that IgG Fcγ receptor II-b (FcγRIIb) mediates Aβ neurotoxicity and neurodegeneration. We found that FcγRIIb is significantly upregulated in the hippocampus of AD brains and neuronal cells exposed to synthetic Aβ. Neuronal FcγRIIb activated ER stress and caspase-12, and Fcgr2b KO primary neurons were resistant to synthetic Aβ-induced cell death in vitro. Fcgr2b deficiency ameliorated Aβ-induced inhibition of long-term potentiation and inhibited the reduction of synaptic density by naturally secreted Aβ. Moreover, genetic depletion of Fcgr2b rescued memory impairments in an AD mouse model. To determine the mechanism of action of FcγRIIb in Aβ neurotoxicity, we demonstrated that soluble Aβ oligomers interact with FcγRIIb in vitro and in AD brains, and that inhibition of their interaction blocks synthetic Aβ neurotoxicity. We conclude that FcγRIIb has an aberrant, but essential, role in Aβ-mediated neuronal dysfunction.

show abstract

Identification of FcγRI, II and III on normal human brain ramified microglia and on microglia in senile plaques in Alzheimer's disease

Cited by 98 publications

References 23 publications

Recombinant humanised anti-HER2/neu antibody (Herceptin®) induces cellular death of glioblastomas

Recombinant humanised anti-HER2/neu antibody (Herceptin®) induces cellular death of glioblastomas

3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors Attenuate β-Amyloid-Induced Microglial Inflammatory Responses

FcγRIIb mediates amyloid-β neurotoxicity and memory impairment in Alzheimer’s disease

Contact Info

Product

Resources

About