Radioimmunotherapy of Cryptococcus neoformans spares bystander mammalian cells

Ruth A. Bryan, Zewei Jiang, Alfred Morgenstern, Frank Bruchertseifer, Arturo Casadevall, Ekaterina Dadachova

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Aim: Previously, we showed that radioimmunotherapy (RIT) for cryptococcal infections using radioactively labeled antibodies recognizing the cryptococcal capsule reduced fungal burden and prolonged survival of mice infected with Cryptococcus neoformans. Here, we investigate the effects of RIT on bystander mammalian cells. Materials & methods: Heat-killed C. neoformans bound to anticapsular antibodies, unlabeled or labeled with the α-emitter rhenium-188 (16.9-h half-life) or the α-emitter bismuth-213 (46-min half-life), was incubated with macrophage-like J774.16 cells or epithelial-like Chinese hamster ovary cells. Lactate dehydrogenase activity, crystal violet uptake, reduction of tetrazolium dye (2,3)-bis-(2-methoxy-4-nitro-5-sulfenyl)- (2H)-terazolium-5-carboxanilide and nitric oxide production were measured. Results: The J774.16 and Chinese hamster ovary cells maintained membrane integrity, viability and metabolic activity following exposure to radiolabeled C. neoformans.Conclusion: RIT of C. neoformans is a selective therapy with minimal effects on host cells and these results are consistent with observations that RIT-treated mice with cryptococcal infection lacked RIT-related pathological changes in lungs and brain tissues.

Original languageEnglish (US)
Pages (from-to)1081-1089
Number of pages9
JournalFuture Microbiology
Volume8
Issue number9
DOIs
StatePublished - Sep 1 2013

Keywords

  • Cryptococcus neoformans
  • NO production
  • bystander effects
  • fungal infection
  • particulate radiation
  • radioimmunotherapy

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

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    Bryan, R. A., Jiang, Z., Morgenstern, A., Bruchertseifer, F., Casadevall, A., & Dadachova, E. (2013). Radioimmunotherapy of Cryptococcus neoformans spares bystander mammalian cells. Future Microbiology, 8(9), 1081-1089. https://doi.org/10.2217/fmb.13.79