期刊
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
卷 6, 期 3, 页码 -出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/NXI.0000000000000550
关键词
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资金
- USA National Multiple Sclerosis Society
- Melissa and Paul Anderson Endowment at the University of Pennsylvania
- Research Foundation of the MS Society of Canada
- Parker Webber Chair in Neurology Endowment (DMC Foundation/Wayne State University School of Medicine)
- NIH [P30 ES020957, P30 CA 022453, S10 OD010700]
Objective To identify whether factors toxic to oligodendrocytes (OLs), released by B cells from patients with MS, are found in extracellular microvesicles enriched in exosomes. Methods Conditioned medium (Sup) was obtained from cultures of blood B cells of patients with MS and normal controls (NCs). Exosome-enriched (Ex-En) fractions were prepared by solvent precipitation from Sup containing bovine serum and from serum-free Sup by ultracentrifugation (UC) or immunoprecipitation (IP) with antibodies to CD9. Ex-En fractions were diluted 1:4 with OL culture medium and screened for toxic effects on cultured rat OLs as measured by trypan blue uptake. Proteomic analysis was performed on Sup fractions. Results MS B cell-derived Ex-En fractions prepared from Sup by solvent extraction, UC, or IP induced OL death, whereas corresponding Ex-En fractions from NC showed little toxicity. Proteomic analysis of Sup demonstrated enrichment of proteins characteristic of exosomes from both NC and MS B-cell Sup. Ontology enrichment analysis suggested differences in the types and cargo of exosomes from MS Sup compared with NC, with proteins related to cell surface, extracellular plasma membrane, and gliogenesis enriched in MS. Conclusions Much of the in vitro toxicity of Sup from B cells of patients with relapsing-remitting MS is found in Ex-En fractions, as confirmed by 3 methods. Proteomic analysis of B-cell Sup indicates multiple differences between MS and NC.
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