Mechanisms underlying Mannheimia haemolytica leukotoxin-induced oncosis and apoptosis of bovine alveolar macrophages

Praveen Thumbikat, Dileepan T, Mathur S Kannan, Samuel K. Maheswaran

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Mannheimia (Pasteurella) haemolytica leukotoxin (LktA) binds to the bovine β2 integrins (such as LFA-1 - CD11a/CD18) and leads to subsequent cellular effects in a dose dependent manner. The objectives of this study were to delineate the mechanisms that underlie LktA-induced oncosis and apoptosis and to examine the role of LktA/LFA-1 interaction in these events. The results demonstrate that LktA-induced oncosis proceeds through a LFA-1 and caspase-1 dependent pathway referred to as 'pyrotosis', as well as through a LFA-1- and caspase-1-independent pathway. LktA-induced apoptosis in alveolar macrophages involves activation of caspase-3 and engages the extrinsic and intrinsic pathways of apoptosis, with the extrinsic pathway being dependent on LFA-1 signaling and TNFα.

Original languageEnglish (US)
Pages (from-to)161-172
Number of pages12
JournalMicrobial Pathogenesis
Volume38
Issue number4
DOIs
StatePublished - Apr 2005

Bibliographical note

Funding Information:
This study was supported by funds from USDA-NRICG (2000–35204–9230) and the Minnesota Agricultural Experiment Station. We thank Charles J. Czuprynski from the Department of Pathobiological Sciences, University of Wisconsin for helpful discussions.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Apoptosis
  • Caspase-8
  • Mannheimia haemolytica leukotoxin
  • Oncosis
  • Pore formation
  • Pyrotosis

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