In vitro induction of hepatocyte synthesis of the acute phase reactant mouse serum amyloid P-component by macrophages and IL 1

Abstract

The in vitro culture conditions for the induction and synthesis of the mouse acute phase reactant, serum amyloid P-component (SAP), were established using isolated hepatocytes. SAP synthesis was five to eight times greater with hepatocytes isolated from mice during the acute phase of inflammation vs. hepatocytes obtained from untreated mice. The induction of SAP synthesis in normal hepatocytes for LPS-unresponsive mice was macrophage dependent. Activated macrophages provided the most "helper" activity for SAP production. Partially purified mouse IL 1 from the P388D1 macrophage line also induced SAP synthesis. Only four IL 1 units/ml were required for optimal SAP induction. The addition of IL 1 in the presence of elicited macrophages provided an additive effect on hepatocyte SAP synthesis. The SAP-inducing activity of IL 1 copurified with its thymocyte-stimulating activity and was associated with a 11 to 25-Kd MW polypeptide. Phenylglyoxal treatment of IL 1 inactivated its thymocyte stimulating activity but not its SAP inducing potential. Inhibition of m-RNA synthesis, protein synthesis, N-glycosylation, and protein secretion effectively prevented in vitro hepatocyte SAP production.