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


RESULTS
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
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.
Guo
Ya-Lan
YL
Institute for Virology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Jiangsu, People's Republic of China.
Liu
Dan-Qing
DQ
Bian
Zhen
Z
Zhang
Chen-Yu
CY
Zen
Ke
K
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000382:microbiology; D051928:CD47 Antigen / Q000096:biosynthesis*; D015536:Down-Regulation; D019453:Escherichia coli O157 / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006463:Hemolytic-Uremic Syndrome / Q000378:metabolism* / Q000382:microbiology*; D019041:L-Selectin / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015539:Platelet Activation; D011971:Receptors, Immunologic / Q000378:metabolism; D013921:Thrombocytopenia / Q000378:metabolism* / Q000382:microbiology*
D051928:CD47 Antigen; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic; D019041:L-Selectin