Mechanisms underlying Mannheimia haemolytica leukotoxin-induced oncosis and apoptosis of bovine alveolar macrophages.
Mannheimia (Pasteurella) haemolytica leukotoxin (LktA) binds to the bovine beta2 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 TNFalpha.
Thumbikat
Praveen
P
Department of Veterinary and Biomedical Sciences, University of Minnesota, St.Paul, MN 55108, USA.
Dileepan
Thamotharampillai
T
Kannan
Mathur S
MS
Maheswaran
Samuel K
SK
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001426:Bacterial Proteins / Q000502:physiology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002417:Cattle; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005098:Exotoxins / Q000502:physiology*; D006460:Hemolysin Proteins / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D016676:Macrophages, Alveolar / Q000382:microbiology* / Q000473:pathology; D016978:Mannheimia haemolytica / Q000502:physiology*; D008856:Microscopy, Fluorescence; D012766:Pasteurellosis, Pneumonic / Q000382:microbiology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D001426:Bacterial Proteins; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D005098:Exotoxins; D006460:Hemolysin Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha; C102677:lktA protein, bacteria; D020169:Caspases