Selectins mediate the adhesion of leukocytes to activated endothelial cells and activated platelets. In addition to these cell-to-cell interactions, they influence the
fibrin content and size of venous thrombi in different animal models. However, the exact role of
selectins in human
endotoxemia still remains unclear. We aimed to investigate the effect of
selectin inhibition in
lipopolysaccharide (LPS)-induced
tissue factor (TF)-dependent activation of coagulation in a well-standardized model of human
endotoxemia. To explore whether
selectin blockade attenuates LPS-induced coagulation in humans, we performed a randomized, double-bind placebo-controlled crossover trial in 16 healthy male volunteers. All subjects received 2 ng/kg of LPS and, 10 min thereafter, a 15-min infusion of either 30 mg/kg of the pan-
selectin antagonist
bimosiamose or equal volumes of placebo in random order, with a washout period of 6 weeks between both periods. Treatment with
bimosiamose had no significant effect on LPS-induced TF expression, as quantified by TF
mRNA levels, or on LPS-induced coagulation response, reflected by increases in plasma
thrombin-
antithrombin (TAT) complexes and
prothrombin fragment (F1 + 2) levels. Furthermore,
bimosiamose did not affect the LPS-dependent changes in leukocyte subpopulations or the increase in platelet-leukocyte aggregates, as determined in the level of CD41+ monocytes. Finally, neither the LPS-induced release of
tumor necrosis factor,
interleukin 6, leukocyte expression of CD11b, nor
intercellular adhesion molecule 1 were affected by administration of
bimosiamose. The pan-
selectin antagonist
bimosiamose does not attenuate TF-triggered coagulation or
inflammation in human
endotoxemia. This indicates a minor influence of this
selectin antagonist in this model. In addition, infusion of
bimosiamose was safe and well tolerated in human
endotoxemia.