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.
Bibliographical noteFunding 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 2017 Elsevier B.V., All rights reserved.
- Mannheimia haemolytica leukotoxin
- Pore formation