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PMID:16514062

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Citation

Ståhl, AL, Svensson, M, Mörgelin, M, Svanborg, C, Tarr, PI, Mooney, JC, Watkins, SL, Johnson, R and Karpman, D (2006) Lipopolysaccharide from enterohemorrhagic Escherichia coli binds to platelets through TLR4 and CD62 and is detected on circulating platelets in patients with hemolytic uremic syndrome. Blood 108:167-76

Abstract

This study presents evidence that human platelets bind lipopolysaccharide (LPS) from enterohemorrhagic Escherichia coli (EHEC) through a complex of toll-like receptor 4 (TLR4) and CD62, leading to their activation. TLR4 colocalized with CD62 on the platelet membrane, and the TLR4 specificity of LPS binding to platelets was confirmed using C57BL/10ScN mice lacking Tlr4. Only platelets from TLR4 wild-type mice bound O157LPS in vitro. After in vivo injection, O157LPS bound to platelets from wild-type mice, which had lower platelet counts than did mice lacking TLR4. Mouse experiments confirmed that O157LPS binding to TLR4 is the primary event leading to platelet activation, as shown by CD40L expression, and that CD62 further contributes to this process. Activation of human platelets by EHEC-LPS was demonstrated by expression of the activated GPIIb/IIIa receptor, CD40L, and fibrinogen binding. In perfusion experiments, platelet activation on endothelial cells was TLR4 and CD62 dependent. O157LPS was detected on platelets from 12 of 14 children with EHEC-associated hemolytic uremic syndrome (HUS) and on platelets from 2 children before the development of HUS but not on platelets of EHEC-infected children in whom HUS did not develop (n = 3). These data suggest that O157LPS on platelets might contribute to platelet consumption in HUS.

Links

PubMed PMC1895830 Online version:10.1182/blood-2005-08-3219

Keywords

Adolescent; Adult; Animals; Blood Platelets/immunology; Child; Child, Preschool; Escherichia coli O157/immunology; Female; Hemolytic-Uremic Syndrome/blood; Hemolytic-Uremic Syndrome/immunology; Humans; Infant; Lipopolysaccharides/immunology; Male; Mice; P-Selectin/immunology; Protein Binding/immunology; Toll-Like Receptor 4/immunology

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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