PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis.
Activated glial cells are implicated in regulating and effecting the immune response that occurs within the CNS as part of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). The peripheral benzodiazepine receptor (PBR) is expressed in glial cells. We examined the utility of using in vitro and in vivo ligand binding to the PBR as a measure of lesion activity in autoimmune CNS demyelinating diseases. Applying a combined autoradiography and immunohistochemical approach to spinal cord and brain tissues from mice with EAE, we found a correlation at sites of inflammatory lesions between [3H]-PK11195 binding and immunoreactivity for the activated microglial/macrophage marker Mac-1/CD11b. In MS tissues, [3H]-PK11195 binding correlated with sites of immunoreactivity for the microglial/macrophage marker CD68, at the edges of chronic active plaques. Positron emission tomography (PET) imaging with [11C]-PK11195 showed ligand uptake only at sites of active MS lesions defined by magnetic resonance imaging criteria. Our results indicate the potential to develop markers suitable for both in vitro and in vivo use, which will serve to help correlate phenotypic and functional properties of cells which participate in disease or injury responses within the CNS.
Vowinckel
E
E
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Quebec, Canada.
Reutens
D
D
Becher
B
B
Verge
G
G
Evans
A
A
Owens
T
T
Antel
J P
JP
D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008578:Meninges / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D017628:Microglia / Q000502:physiology*; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D011963:Receptors, GABA-A / Q000378:metabolism*; D012016:Reference Values; D014055:Tomography, Emission-Computed
D015415:Biomarkers; D007546:Isoquinolines; D011963:Receptors, GABA-A; C037850:PK 11195