ABSTRACT

This chapter demonstrates that Kupffer Cells (KC) can provide the signal for Acute-Phase Protein (APP) synthesis in vivo and in vitro. KC supernatants in the presence of glucocorticoids have previously been shown to be capable of inducing alpha-2-macroglobulin synthesis. The chapter also demonstrates that lipopolysaccharide (LPS)-treated KC induce a significant depression in total HC protein synthesis, thereby demonstrating that KC could lead to alterations in HC protein metabolism. This inhibition in protein synthesis can be reversed by the addition of dexamethasone. The close association of KC and HC in coculture approximates the interactions that normally exist in the liver parenchyma. The chapter examines several facets of this response, including the numbers of KC needed to alter HC APP synthesis (KC:HC ratios), the response of the coculture model to LPS and other cytokines, and the effect of glucocorticoids on this response. Thus, the synthesis of APP by HC has been characterized in her KC:HC model.