Caspase activation during Haemophilus somnus lipooligosaccharide-mediated apoptosis of bovine endothelial cells.
Vasculitis is commonly seen during systemic Haemophilus somnus infections. Although, the mechanism of vascular damage is not completely understood, in a previous report we demonstrated that H. somnus and its lipooligosaccharide (LOS) induced apoptosis in bovine pulmonary artery endothelial cells in vitro. In the present study, we investigated the role of caspase activation in LOS-mediated apoptosis of bovine endothelial cells. Exposure to H. somnus LOS induced caspase-3 activation and chromatin condensation in endothelial cells. These responses were blocked by the addition of a pan-caspase inhibitor (z-VAD-fmk) or capase-3 inhibitor (DEVD-fmk). Incubation of endothelial cells with H. somnus LOS also induced activation of the initiator caspases, caspases-8 and 9, with the activity of the former increasing more rapidly than the latter. Addition of a caspase-8 inhibitor (IETD-fmk) significantly reduced LOS-mediated apoptosis, whereas, addition of a caspase-9 inhibitor (LEHD-fmk) had little effect. These data suggest that LOS-mediated activation of caspase-3 and apoptosis of endothelial cells is caspase-8 dependent.
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive West, Madison, WI 63706, USA.
Matt J
MJ
Sylte
Fabio P
FP
Leite
Chris J
CJ
Kuckleburg
Thomas J
TJ
Inzana
Charles J
CJ
Czuprynski
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D002843:Chromatin / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000201:enzymology / Q000502:physiology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044138:Haemophilus somnus / Q000276:immunology* / Q000472:pathogenicity; D008070:Lipopolysaccharides / Q000633:toxicity*; D009842:Oligopeptides / Q000494:pharmacology
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D002843:Chromatin; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009842:Oligopeptides; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C425644:isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone; C023023:lipid-linked oligosaccharides; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases