Endotoxin-induced effects on platelets and monocytes in an in vivo model of inflammation.
OBJECTIVE
Chronic inflammation is a major contributing factor to atherosclerosis and various markers of inflammation, fibrinolysis and coagulation are upregulated in patients with established atherosclerotic disease. The aim of this study was to investigate the direct and short-term effects of inflammation on platelet and monocyte activation with an in vivo model of endotoxemia in healthy volunteers.


RESULTS
In this study, 13 healthy male subjects with a mean age of 29.5+/-5.4 years received intravenous administration of lipopolysaccharide (LPS; 20 IU/kg IV). The kinetics of CD40-ligand and CD62P expression on platelets, tissue-factor binding on monocytes and platelet-monocyte aggregates were measured by whole blood flow cytometry at baseline and at 1, 2, 4, 6 and 24 hours after LPS administration. Plasma levels of soluble CD40-ligand were measured with an ELISA over the same time course. Platelet-monocyte aggregates, tissue-factor binding on monocytes and surface expression of platelet CD40L significantly increased in experimental endotoxemia in vivo, reaching peak values 1 hour after LPS administration. All values returned to baseline after 24 hours. Surface expression of CD62P on platelets and plasma levels of sCD40L did not change significantly in response to LPS.


CONCLUSIONS
In vivo administration of endotoxin leads to an activation of platelets and monocytes with an upregulation of proatherogenic CD40L on platelets. These findings underpin the role of inflammation in early atherogenesis through platelet and monocyte activation in an in vivo model.
Kälsch
Thorsten
T
1st Department of Medicine, University Hospital Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. thorsten.kaelsch@med.ma.uni-heidelberg.de
Elmas
Elif
E
Nguyen
Xuan Duc
XD
Suvajac
Nenad
N
Klüter
Harald
H
Borggrefe
Martin
M
Dempfle
Carl-Erik
CE
D000328:Adult; D050197:Atherosclerosis / Q000139:chemically induced / Q000276:immunology; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D019446:Endotoxemia / Q000139:chemically induced* / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology; D013925:Thromboplastin / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D008070:Lipopolysaccharides; D019007:P-Selectin; D023201:CD40 Ligand; D013925:Thromboplastin