PLoS ONE (Jan 2009)

Down-regulation of platelet surface CD47 expression in Escherichia coli O157:H7 infection-induced thrombocytopenia.

  • Ya-Lan Guo,
  • Dan-Qing Liu,
  • Zhen Bian,
  • Chen-Yu Zhang,
  • Ke Zen

DOI
https://doi.org/10.1371/journal.pone.0007131
Journal volume & issue
Vol. 4, no. 9
p. e7131

Abstract

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BACKGROUND: Platelet depletion is a key feature of hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) infection. The mechanism underlying STEC-induced platelet depletion, however, is not completely understood. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrated for the first time that platelet surface expression of CD47 was significantly decreased in C57BL6 mice treated with concentrated culture filtrates (CCF) from STEC O157:H7. STEC O157:H7 CCF treatment also led to a sharp drop of platelet counts. The reduction of cell surface CD47 was specific for platelets but not for neutrophil, monocytes and red blood cells. Down-regulation of platelet surface CD47 was also observed in isolated human platelets treated with O157:H7 CCF. Platelet surface CD47 reduction by O157:H7 CCF could be blocked by anti-TLR4 antibody but not anti-CD62 antibody. Down-regulation of platelet surface CD47 was positively correlated with platelet activation and phagocytosis by human monocyte-derived macrophages. Furthermore, the enhanced phagocytosis process of O157:H7 CCF-treated platelets was abolished by addition of soluble CD47 recombinants. CONCLUSIONS/SIGNIFICANCE: Our results suggest that platelet CD47 down-regulation may be a novel mechanism underneath STEC-induced platelet depletion, and that the interactions between CD47 and its receptor, signal regulatory protein alpha (SIRPalpha), play an essential role in modulating platelet homeostasis.