Staphylococcal enterotoxin B initiates protein kinase C translocation and eicosanoid metabolism while inhibiting thrombin-induced aggregation in human platelets.
Staphylococcal enterotoxin (SE) B, a heat-stable toxin secreted by Staphylococcus aureus, has been implicated in the pathogenesis and exacerbation of several critical illnesses. It has been hypothesized that enterotoxins may interact with blood products such as platelets, in addition to T-lymphocytes and renal proximal tubule cells. The aim of this present study was to elucidate whether SEB directly alters human platelet function. Human platelet rich plasma (PRP) was pre-incubated with SEA, SEB, SEC or TSST-1, (at various concentrations and incubation times). After incubation, PRP was exposed to thrombin and aggregation was assessed. Incubation with all toxins tested resulted in decreased aggregation, specifically; exposure to 10mu g/ml of SEB for 30 min caused a 20% decrease and a 49% decrease at 90 min. A similar reduction in aggregation was seen in samples incubated with phorbol myristate acetate, a known stimulator of protein kinase C (PKC). Further, platelets exposed to SEB exhibited an increased plasma membrane PKC activity. Sphingosine, an inhibitor of PKC proved to block the SEB-induced reduction in aggregation. SEB effects on platelet metabolism were investigated using high performance liquid chromatography showing up to a 2-fold increase of active metabolites lipoxin A4 and 12-HETE, as compared to control. These data indicate that SEB is able to induce platelet dysfunction, and these effects may be mediated through activation of PKC.
Department of Molecular Pathology, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, Maryland 20910, USA.
Uyen
U
Tran
Thomas
T
Boyle
Jeffrey W
JW
Shupp
Rasha
R
Hammamieh
Marti
M
Jett
D016718:Arachidonic Acid / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D004768:Enterotoxins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013997:Time Factors
D015777:Eicosanoids; D004768:Enterotoxins; D016718:Arachidonic Acid; C031818:enterotoxin B, staphylococcal; D011493:Protein Kinase C; D013917:Thrombin