6533b7cffe1ef96bd1259a5b
RESEARCH PRODUCT
Targeting CD52 does not affect murine neuron and microglia function.
Christina F. VogelaarCarlos MaldetDirk LuchtmanErik EllwardtStefan BittnerSamantha Schmaulsubject
0301 basic medicineEncephalomyelitis Autoimmune ExperimentalCD52Excitotoxicitymedicine.disease_causeNeuroprotection03 medical and health sciencesMice0302 clinical medicinemedicineAnimalsAlemtuzumabPharmacologyNeuronsMicrogliabusiness.industryMultiple sclerosisExperimental autoimmune encephalomyelitismedicine.disease030104 developmental biologymedicine.anatomical_structureCD52 AntigenGene Expression RegulationAlemtuzumabCalciumNeuronMicrogliabusinessNeuroscience030217 neurology & neurosurgerymedicine.drugdescription
The humanized anti-CD52 antibody alemtuzumab is successfully used in the treatment of multiple sclerosis (MS) and is thought to exert most of its therapeutic action by depletion and repopulation of mainly B and T lymphocytes. Although neuroprotective effects of alemtuzumab have been suggested, direct effects of anti-CD52 treatment on glial cells and neurons within the CNS itself have not been investigated so far. Here, we show CD52 expression in murine neurons, astrocytes and microglia, both in vitro and in vivo. As expected, anti CD52-treatment caused profound lymphopenia and improved disease symptoms in mice subjected to experimental autoimmune encephalomyelitis (EAE). CD52 blockade also had a significant effect on microglial morphology in organotypic hippocampal slice cultures but did not affect microglial functions. Furthermore, anti-CD52 neither changed baseline neuronal calcium, nor did it act neuroprotective in excitotoxicity models. Altogether, our findings argue against a functionally significant role of CD52 blockade on CNS neurons and microglia. The beneficial effects of alemtuzumab in MS may be exclusively mediated by peripheral immune mechanisms.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-03-01 | European journal of pharmacology |