Investigation of the effect of tumor necrosis factor alpha on platelets of saline - or lipopolysaccharide - injected rats

Abstract

Evidence indicates that platelets have an important role in sepsis. In fact, sepsis severity is positively correlated to thrombocytopenia and platelet activity. In sepsis high formation of inflammatory mediators such as tumor necrosis factor-alpha (TNF-±) occurs, besides nitric oxide (NO) and reactive oxygen species (ROS) generation, which contribute to tissue injuries that may culminate in multiple organ dysfunction, especially lungs, liver and kidneys. Lipopolysaccharide (LPS) is commonly used as a tool to study sepsis, since its administration into animals and humans leads to several signals observed in septic condition as increased inflammatory cytokines production such as TNF-±, which is the first one liberated in sepsis. Previous works of our group showed that the incubation of LPS from E. coli did not modify platelet function directly; however, it was significantly reduced in LPS-injected rats. Moreover, in platelets of LPS-injected rats ROS production was largely increased via NADPH oxidase activation. Works have shown that TNF-± activates NADPH oxidase in different cells although investigation of the effect of this cytokine on platelets is rare. Therefore, the objective of the present work is to investigate the effect of TNF-± on platelet adhesion and on aggregation in vitro. Furthermore, we will investigate the TNF-± role in platelet aggregation inhibition and in the increased intraplatelet ROS generation in LPS-treated rats. Finally, we are going to evaluate the effect of platelets from LPS-injected rats in the viability of endothelial cells. (AU)