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Thromb Haemost 2003; 90(05): 872-881
DOI: 10.1160/TH03-02-0085
Platelets and Blood Cells
Schattauer GmbH

Mechanisms of the priming effect of low doses of lipopolysaccharides on leukocyte-dependent platelet aggregation in whole blood

Giuseppe Montrucchio
1   Department of Clinical Pathophysiology, University of Turin, Italy
,
Ornella Bosco
1   Department of Clinical Pathophysiology, University of Turin, Italy
,
Lorenzo Del Sorbo
1   Department of Clinical Pathophysiology, University of Turin, Italy
,
Paolo Fascio Pecetto
1   Department of Clinical Pathophysiology, University of Turin, Italy
,
Enrico Lupia
1   Department of Clinical Pathophysiology, University of Turin, Italy
,
Alberto Goffi
1   Department of Clinical Pathophysiology, University of Turin, Italy
,
Paola Omedè
2   Division of Hematology, University of Turin, Italy
,
Giorgio Emanuelli
1   Department of Clinical Pathophysiology, University of Turin, Italy
,
Giovanni Camussi
3   Department of Internal Medicine, University of Turin, Italy
4   Center for Experimental Research and Medical Studies (CERMS), Azienda Ospedaliera S. Giovanni Battista, Turin, Italy
› Author AffiliationsFinancial support: This work was supported by the CNR targeted project Biotechnology (to G.C.), MIUR Cofin 2001 (to G.C.), and Fondi Ateneo 60% (to G.C. and G.M.).
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Publication History

Received 07 February 2003

Accepted after resubmission 29 July 2003

Publication Date:
05 December 2017 (online)

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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 mechanisms involved in the aggregation of platelets and in their interaction with leukocytes in whole blood after stimulation with low 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. As shown by cytofluorimetry, platelets neither bind FITC-LPS, nor express the LPS-receptors CD14 and toll-like receptor 4 (TLR4). On the contrary, LPS primed monocytes and to a lesser extent polymorphonuclear neutrophils to adhere to platelets. Both platelet-leukocyte interaction and platelet aggregation in whole blood were inhibited by blockade of CD14 and TLR4. Moreover, the interaction between platelets and leukocytes was inhibited by P-selectin, and by blockade of PAF and reactive oxygen species, suggesting a role of P-selectin and of leukocyte-derived mediators.

In conclusion, these results elucidate the mechanisms leading to platelet activation and interaction with leukocytes triggered by LPS. They suggest that the activation of platelets by LPS is mainly dependent on leukocytes and especially monocytes as a result of CD14 and TLR4 engagement. Moreover, we found that leukocyte-platelet interaction was triggered by the synthesis of PAF and the generation of oxygen radicals that induced upregulation of surface expression of P-selectin.

Keywords

Monocytes - platelet-activating factor - radical oxygen - CD14 - P-selectin - TLR-4
 

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