Aspartic protease and caspase 3/7 activation are central for macrophage apoptosis following infection with Escherichia coli

Lee Albee, Bo Shi, Harris Perlman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Macrophages are vital for host defense against microbial infections. We have previously shown that infection of macrophages with a non-pathogenic strain of Escherichia coli induces apoptosis rapidly. Here, we demonstrate that infection of macrophages results in the activation of caspases prior to the induction of the intrinsic apoptosis pathway. Caspases 9 and 3 are activated prior to the release of intermembrane mitochondrial protein cytochrome C into the cytosol in infected macrophages. Treatment with an inhibitor to caspase 9 has no effect on the death of macrophages and does not prevent activation of the downstream effector caspase 3/7. In contrast, an inhibitor to caspase 3/7 reduces cell death in E. coli-infected macrophages. Although caspase 9 is not required, activation of aspartic proteases, of which cathepsin D is one of the central members, is essential for activation of caspase 3/7. Treatment with pepstatin A, an inhibitor of aspartic proteases, markedly diminishes the activation of cathepsin D and caspase 3/7 and reduces death in E. coli-infected macrophages. Collectively, these data suggest that cathepsin D activation of caspase 3/7 may be required for inducing one of the death pathways elicited by E. coli.

Original languageEnglish (US)
Pages (from-to)229-237
Number of pages9
JournalJournal of Leukocyte Biology
Volume81
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • Bacteria
  • Bcl-2
  • Lysosomal
  • Mitochondria

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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