DIFFERENTIAL UP-REGULATION OF CERULOPLASMIN GENE-EXPRESSION IN RAT IMMUNE TISSUES DURING EXPERIMENTAL INFLAMMATION

We have investigated whether rat immune tissues (spleen, thymus and bo ne marrow) contain a full-length ceruloplasmin (Cp) mRNA identical to that in rat hepatocytes and if this extrahepatic Cp mRNA is up-regulat ed in response to inflammation. Experimental inflammation was induced by intraperitoneal administration of lipopolysaccharide (LPS), and was characterized by decreased (50%) food intake and a two-fold increase in serum Cp oxidase activity. Tissues were collected 24 h after LPS or saline injection (controls). Primer pairs spanning either exons 1-5 o r exons 17-19 of rat liver Cp mRNA were selected for RT-PCR reactions; with total RNA isolated from intact spleen, freshly-isolated splenic mononuclear cells (MNC), thymus, and bone marrow. RT-PCR products iden tical to those of rat liver tissue were generated suggesting the prese nce of a full-length Cp mRNA in these immune tissues. Northern analysi s revealed that a 3.7 kb mRNA was present in both liver and intact spl een, but was barely detectable in the thymus. Densitometric analysis i ndicated that the abundance of splenic Cp mRNA was about 3% that of li ver Cp mRNA per unit of total tissue RNA. LPS-induced inflammation inc reased Cp mRNA in liver and spleen tissues by 90% and 80%, respectivel y, but had little impact on Cp mRNA content in thymus. Additional stud ies are needed to define the role(s) of splenic Cp gene expression and copper in host defense. (C) 1998 Elsevier Science Inc.