title: Shiga toxin 2 and lipopolysaccharide cause monocytic THP-1 cells to release factors which activate platelet function.
abstract: 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 causedTHP-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 byTHP-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.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
authors.forename: Fadila
authors.initials: F
authors.lastname: Guessous
authors.forename: Marek
authors.initials: M
authors.lastname: Marcinkiewicz
authors.forename: Renata
authors.initials: R
authors.lastname: Polanowska-Grabowska
authors.forename: Tiffany R
authors.initials: TR
authors.lastname: Keepers
authors.forename: Tom
authors.initials: T
authors.lastname: Obrig
authors.forename: Adrian R L
authors.initials: AR
authors.lastname: Gear
mesh_terms: D001792:Blood Platelets / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D054422:Chemokine CCL22; D018946:Chemokine CCL5 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007938:Leukemia; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010974:Platelet Aggregation / Q000502:physiology*; D022641:Shiga Toxin 2 / Q000494:pharmacology*
chemical_list: C515482:CCL22 protein, human; D054422:Chemokine CCL22; D018946:Chemokine CCL5; D019742:Chemokines, CC; D016209:Interleukin-8; D008070:Lipopolysaccharides; D022641:Shiga Toxin 2