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Type: Journal article
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
Author: Kraemer, B.
Campbell, R.
Schwertz, H.
Franks, Z.
De Abreu, A.
Grundler, K.
Kile, B.
Dhakal, B.
Rondina, M.
Kahr, W.
Mulvey, M.
Blaylock, R.
Zimmerman, G.
Weyrich, A.
Citation: Blood, 2012; 120(25):5014-5020
Publisher: American Society of Hematology
Issue Date: 2012
ISSN: 0006-4971
Statement of
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.
Keywords: Blood Platelets
Rights: © 2012 by The American Society of Hematology
RMID: 0030100561
DOI: 10.1182/blood-2012-04-420661
Appears in Collections:Medicine publications

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