The lack of expression of the peripheral benzodiazepine receptor characterises microglial response in anaplastic astrocytomas
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The peripheral benzodiazepine receptor (PBR) is a 18 kDa molecule mainly involved in cholesterol transport through the mitochondrial membrane. In microglia, PBR is expressed from the earliest stages of activation and appears to exert a pro-inflammatory function. This molecule is commonly up-regulated in inflammatory, degenerative, infective and ischaemic lesions of the central nervous system but it has never been reported in glioma-infiltrating microglia. We examined two anaplastic astrocytomas showing minimal contrast-enhancement and therefore little damage of the blood brain barrier to minimise the presence of blood borne macrophages within tumour tissue. The two lesions were studied in vivo using positron emission tomography (PET) with the specific PBR ligand [11C](R)-PK11195 and the corresponding tumour tissue was investigated with an anti-PBR antibody. Glioma-infiltrating microglia were characterised for molecules involved in antigen presentation and cytotoxic activity. As comparison, PBR was investigated in three brains with multiple sclerosis (MS) and three with Parkinson’s disease (PD). The expression profile of four anaplastic astrocytomas was also exploited and results were compared to the profile of eleven samples of normal temporal lobe and nine cases of PD. PET studies showed that [11C](R)-PK11195 binding was markedly lower in tumours than in the contralateral grey matter. Pathological investigation revealed that glioma-infiltrating microglia failed to express PBR and cytotoxic molecules although some cells still expressed antigen presenting molecules. PBR and cytotoxic molecules were highly represented in MS and PD. Evaluation of microarray datasets confirmed these differences. Our results demonstrated PBR suppression in glioma-infiltrating microglia and suggested that PBR may have a relevant role in modulating the anti-tumour inflammatory response in astrocytic tumours.
KeywordsAstrocytoma Microglia Peripheral benzodiazepine receptor PK11195 Positron emission tomography
This study was supported by a Grant-in-Aid for Scientific Research on Priority Areas (17022023) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. Dr. Roncaroli’s research is partly supported by the Charity BRTC. We thank Dr. Nobuhiro Mikuni from the Department of Neurosurgery at the Kyoto University Graduate School of Medicine for recruiting the patients, Ms. Lynne Christian from the Department of Neuropathology at the Imperial College in London for critically reviewing the manuscript, Professor Graeber and Dr. Moran, Department of Neuropathology, Imperial College for kindly making available their dataset generated with cases of Parkinson’s Disease.
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