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|Title:||Bacteria differentially induce degradation of Bcl-xL, a survival protein, by human platelets|
|Other Titles:||Bacteria differentially induce degradation of Bcl-x<inf>L</inf>, a survival protein, by human platelets|
De Abreu, A.
|Citation:||Blood, 2012; 120(25):5014-5020|
|Publisher:||American Society of Hematology|
|Bjoern F. Kraemer, Robert A. Campbell, Hansjorg Schwertz, Zechariah G. Franks, Adriana Vieira de Abreu ... Benjamin T. Kile ... et al.|
|Abstract:||Bacteria can enter the bloodstream in response to infectious insults. Bacteremia elicits several immune and clinical complications, including thrombocytopenia. A primary cause of thrombocytopenia is shortened survival of platelets. We demonstrate that pathogenic bacteria induce apoptotic events in platelets that include calpain-mediated degradation of Bcl-x(L), an essential regulator of platelet survival. Specifically, bloodstream bacterial isolates from patients with sepsis induce lateral condensation of actin, impair mitochondrial membrane potential, and degrade Bcl-x(L) protein in platelets. Bcl-x(L) protein degradation is enhanced when platelets are exposed to pathogenic Escherichia coli that produce the pore-forming toxin α-hemolysin, a response that is markedly attenuated when the gene is deleted from E coli. We also found that nonpathogenic E coli gain degrading activity when they are forced to express α-hemolysin. Like α-hemolysin, purified α-toxin readily degrades Bcl-x(L) protein in platelets, as do clinical Staphylococcus aureus isolates that produce α-toxin. Inhibition of calpain activity, but not the proteasome, rescues Bcl-x(L) protein degradation in platelets coincubated with pathogenic E coli including α-hemolysin producing strains. This is the first evidence that pathogenic bacteria can trigger activation of the platelet intrinsic apoptosis program and our results suggest a new mechanism by which bacterial pathogens might cause thrombocytopenia in patients with bloodstream infections.|
|Rights:||© 2012 by The American Society of Hematology|
|Appears in Collections:||Medicine publications|
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