Modeling of Granule Secretion upon Platelet Activation through the TLR4-Receptor

Abstract

This paper presents the mathematical modeling of the possibility of blood platelets activation by lipopolysaccharides, which are components of the cell wall of gram-negative bacteria, through the toll-like receptor TLR4. We have developed both complete and reduced models of the platelet signaling cascade triggered by TLR4 considering the known kinetics of intracellular signaling enzymes and the contents of the proteins that participate in the TLR4 signaling cascade in human platelets. The results of our simulation show that the concentration of the soluble CD14 protein, which is necessary for the activation of platelets by lipopolysaccharides via TLR4, is insufficient for platelet activation in the blood of healthy donors. Thus, our results suggest that blood platelets can be activated by lipopolysaccharides through TLR4 only in cases of strong activation of the immune system accompanied by an increase in CD14 concentration in the blood.