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https://hdl.handle.net/2440/124982
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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.F. Campbell, R.A. Schwertz, H. Franks, Z.G. De Abreu, A.V. Grundler, K. Kile, B.T. Dhakal, B.K. Rondina, M.T. Kahr, W.H.A. Mulvey, M.A. Blaylock, R.C. Zimmerman, G.A. Weyrich, A.S. |
Citation: | Blood, 2012; 120(25):5014-5020 |
Publisher: | American Society of Hematology |
Issue Date: | 2012 |
ISSN: | 0006-4971 1528-0020 |
Statement of Responsibility: | 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 |
DOI: | 10.1182/blood-2012-04-420661 |
Published version: | http://dx.doi.org/10.1182/blood-2012-04-420661 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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