Endosomal proteolysis precedes ricin A-chain toxicity in macrophages

Maria L. Fiani, Janice S. Blum, Philip D. Stahl

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Ricin A-chain is delivered into macrophages via receptor-mediated endocytosis. We have found that following uptake via the mannose receptor, ricin A-chain is rapidly cleaved by endosomal proteases. Inhibition of endosomal protenses such as cathepsin D and B leads to the accumulation of toxin inside the cell. Inhibition of cathepsin D reduces ricin A-chain cytotoxicity, while blocking cathepsin B enhances cytotoxicity. Similar results were obtained using fibroblasts transfected with the mannose receptor. Our data strongly suggest that the activation or membrane translocation of ricin A-chain is dependent upon the action of specific proteases.

Original languageEnglish (US)
Pages (from-to)225-230
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume307
Issue number2
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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