Shiga toxin 2 and lipopolysaccharide cause monocytic THP-1 cells to release factors which activate platelet function

Fadila Guessous; Marek Marcinkiewicz; Renata Polanowska-Grabowska; Tiffany R. Keepers; Tom Obrig; Adrian R. L. Gear

doi:10.1160/TH05-02-0115

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(05): 1019-1027
DOI: 10.1160/TH05-02-0115

Platelets and Blood Cells

Schattauer GmbH

Shiga toxin 2 and lipopolysaccharide cause monocytic THP-1 cells to release factors which activate platelet function

Fadila Guessous

¹Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA

,

Marek Marcinkiewicz

¹Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA

,

Renata Polanowska-Grabowska

¹Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA

,

Tiffany R. Keepers

²Division of Nephrology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA

,

Tom Obrig

²Division of Nephrology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA

,

Adrian R. L. Gear

¹Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA

› Author Affiliations

Abstract

Summary

Platelet and monocyte activation may contribute to hemolytic anemia, thrombocytopenia and renal failure associated with the hemolytic uremic syndrome (HUS) caused by Escherichia coli O157:H7. Since Shiga toxins (Stxs) and lipopolysaccharide (LPS) from this bacterium are implicated in the pathogenesis of HUS, we examined whether stimulation of THP-1 human monocytic cells by Shiga toxin 2 (Stx2) and LPS can lead to the activation of platelet function. We now show that Stx2 caused THP-1 cells to release the chemokines IL-8, MDC, and RANTES and that the presence of LPS further stimulated this release. IL-8 was produced in greatest amount and was an effective co-agonist for inducing platelet aggregation. Primary human monocytes also released large amounts of IL-8 in response to LPS and Stx2. Factors released by THP-1 cells exposed to Stx2 and LPS activated platelet function as evidenced by increased aggregation, serotonin secretion, P-selectin exposure and by the formation of stable platelet-monocyte aggregates. Our data therefore show that monocytes exposed to E. coli-derived Stx2 and LPS release factors which activate platelet function.

Keywords

Shiga toxin - lipopolysaccharide (LPS) - platelets - aggregation - chemokines - monocytes (THP-1) - secretion - hemolytic uremic syndrome (HUS) - IL-8 - RANTES

Full Text

References

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