Endothelial cell apoptosis induced by bacteria-activated platelets requires caspase-8 and -9 and generation of reactive oxygen species

Christopher J. Kuckleburg, Raksha Tiwari, Charles J. Czuprynski
2008 Thrombosis and Haemostasis  
Acommon feature of severe sepsis is vascular inflammationand damage to theendothelium.Because platelets can be directlyactivatedbybacteria and endotoxin, these cells mayplayanimportantrole in determining theoutcomeofsepsis. Forexample,inhibiting plateleti nteractions witht he endothelium has been shownt oa ttenuate endothelialc elld amage and improve survival during sepsis.Althoughnot entirelyunderstood, theinteractions between bacteria-activated platelets and the endothelium mayp layak ey role
more » ... in the vascular pathologyo fb acterial sepsis. Haemophilus somnus is ab acterial pathogent hat causes diffusev ascular inflammation and endotheliald amage.Ins ome cases H.somnus infection results in an acute and fatalform of vasculitis in thec erebral microvasculaturek nown as thrombotic meningoencephalitis (TME).Inthis study,wehavecharacterized Keywords Histophilus,FasL,R OS,TNFα, Haemophilus somnus the mechanisms involved in endothelialc ella poptosis induced by activatedplatelets.Weobservedthat direct contact between H. somnus-activatedp latelets and endothelialc ells induced significant levels of apoptosis; however, Fas receptor activation on bovine endothelialcells was not able to induce apoptosis unless protein synthesis was disrupted. Endothelialcellapoptosis by H. somnus-activatedplatelets required activation of bothcaspase-8 and caspase-9,as inhibitors of eithercaspase inhibitedapoptosis. Furthermore, activatedp latelets induced endothelialc ellp roduction of reactive oxygens pecies (ROS) and disrupting ROS activityi ne ndothelialc ells significantlyi nhibited apoptosis. Thesefindingssuggestthat bacterialactivation of platelets may contribute to endothelialcelldysfunction observedduring sepsis, specificallybyinducing endothelialcellapoptosis.
doi:10.1160/th07-07-0474 pmid:18278187 fatcat:eltgpv3yxjgtzegz4pfiw4ng5u