Is complement a culprit in infection-induced forms of haemolytic uraemic syndrome?

Johnson, Sally; Waters, Aoife

doi:10.1016/j.imbio.2011.07.022

Cited by 24 publications

(21 citation statements)

References 146 publications

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“…Furthermore, the bacterial components that are being targeted by IgGs-FcγRIIA remain to be identified. Previous literature shows that E. coli secreted Shiga-toxin, which is a virulent factor associated with hemolytic uremic syndrome [34], induces platelet activation [35]. And this might contribute to the formation of platelet thrombi in kidney glomerular capillaries, small arterioles, and arteries [34].…”

Section: Resultsmentioning

confidence: 99%

“…Previous literature shows that E. coli secreted Shiga-toxin, which is a virulent factor associated with hemolytic uremic syndrome [34], induces platelet activation [35]. And this might contribute to the formation of platelet thrombi in kidney glomerular capillaries, small arterioles, and arteries [34]. Additionally, human platelets bind lipopolysaccharide (LPS) from enterohemorrhagic E. coli via toll-like receptor (TLR) 4 and CD62, leading to cell activation [36].…”

Section: Resultsmentioning

confidence: 99%

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Human platelet activation by Escherichia coli: roles for FcγRIIA and integrin αIIbβ3

et al. 2016

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Gram-negative Escherichia coli cause diseases such as sepsis and hemolytic uremic syndrome in which thrombotic disorders can be found. Direct platelet–bacterium interactions might contribute to some of these conditions; however, mechanisms of human platelet activation by E. coli leading to thrombus formation are poorly understood. While the IgG receptor FcγRIIA has a key role in platelet response to various Gram-positive species, its role in activation to Gram-negative bacteria is poorly defined. This study aimed to investigate the molecular mechanisms of human platelet activation by E. coli, including the potential role of FcγRIIA. Using light-transmission aggregometry, measurements of ATP release and tyrosine-phosphorylation, we investigated the ability of two E. coli clinical isolates to activate platelets in plasma, in the presence or absence of specific receptors and signaling inhibitors. Aggregation assays with washed platelets supplemented with IgGs were performed to evaluate the requirement of this plasma component in activation. We found a critical role for the immune receptor FcγRIIA, αIIbβ3, and Src and Syk tyrosine kinases in platelet activation in response to E. coli. IgG and αIIbβ3 engagement was required for FcγRIIA activation. Moreover, feedback mediators adenosine 5’-diphosphate (ADP) and thromboxane A2 (TxA2) were essential for platelet aggregation. These findings suggest that human platelet responses to E. coli isolates are similar to those induced by Gram-positive organisms. Our observations support the existence of a central FcγRIIA-mediated pathway by which human platelets respond to both Gram-negative and Gram-positive bacteria.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Human platelet activation by Escherichia coli: roles for FcγRIIA and integrin αIIbβ3

et al. 2016

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“…TMA may occur in adults and children in the context of invasive Streptococcus pneumoniae infection, and the high morbidity and mortality rate usually reflects the severity of the infection (70,71). In a recently published North American cohort, pneumococcal HUS was most commonly observed in children aged ,2 years with pneumonia and empyema who were extremely unwell and frequently required prolonged hospitalization and intensive care unit admission; the mortality rate was 3%, and 33% developed ESRD (72).…”

Section: Pneumococcal Husmentioning

confidence: 99%

Thrombotic Microangiopathy and the Kidney

Brocklebank

Wood

Kavanagh

2017

CJASN

278

308

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Thrombotic microangiopathy can manifest in a diverse range of diseases and is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ injury, including AKI. It can be associated with significant morbidity and mortality, but a systematic approach to investigation and prompt initiation of supportive management and, in some cases, effective specific treatment can result in good outcomes. This review considers the classification, pathology, epidemiology, characteristics, and pathogenesis of the thrombotic microangiopathies, and outlines a pragmatic approach to diagnosis and management.

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“…Due to its success in these three patients, eculizumab was used to treat more than 300 severe cases in the recent EHEC O104:H4 outbreak in Germany in May 2011 (11). However, data on the outcomes of these patients are still equivocal (12)(13)(14). Despite the widespread use of eculizumab, its effectiveness in the therapy and the role of complement in the pathogenesis of EHEC-associated HUS have not been elucidated so far.…”

mentioning

confidence: 99%

Shiga Toxin 2 Reduces Complement Inhibitor CD59 Expression on Human Renal Tubular Epithelial and Glomerular Endothelial Cells

et al. 2013

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Is complement a culprit in infection-induced forms of haemolytic uraemic syndrome?

Cited by 24 publications

References 146 publications

Human platelet activation by Escherichia coli: roles for FcγRIIA and integrin αIIbβ3

Human platelet activation by Escherichia coli: roles for FcγRIIA and integrin αIIbβ3

Thrombotic Microangiopathy and the Kidney

Shiga Toxin 2 Reduces Complement Inhibitor CD59 Expression on Human Renal Tubular Epithelial and Glomerular Endothelial Cells

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