Summary

Several studies focused on the ability of bacterial lipopolysaccharides(LPS) in triggering platelet and/or leukocyte activation.The aim of this study was to investigate the molecular mechanismsinvolved in the aggregation of platelets and in their interactionwith leukocytes in whole blood after stimulation withlow doses of LPS.LPS did not directly induce platelet aggregation in whole blood,but they primed the aggregation of platelets induced by epinephrine,adenosine diphosphate and arachidonic acid. Asshown by cytofluorimetry, platelets neither bind FITC-LPS, norexpress the LPS-receptors CD14 and toll-like receptor 4(TLR4). On the contrary, LPS primed monocytes and to a lesserextent polymorphonuclear neutrophils to adhere to platlets.Both platelet-leukocyte interaction and platelet aggregationin whole blood were inhibited by blockade of CD14 andTLR4. Moreover, the interaction between platelets and leukocyteswas inhibited by P-selectin, and by blockade of PAF andreactive oxygen species, suggesting a role of P-selectin and ofleukocyte-derived mediators.In conclusion, these results elucidate the mechanisms leading toplatelet activation and interaction with leukocytes triggered byLPS.They suggest that the activation of platelets by LPS is mainlydependent on leukocytes and especially monocytes as aresult of CD14 and TLR4 engagement. Moreover, we found thatleukocyte-platelet interaction was triggered by the synthesis ofPAF and the generation of oxygen radicals that induced upregulationof surface expression of P-selectin.