Cellular specificity of murine renal C3 expression in two models of inflammation.

The expression of the complement protein C3 in extrahepatic tissues is highly regulated during the course of inflammation. Hence, systemic acute phase stimuli such as bacterial lipopolysaccharide (LPS) and autoimmune nephritis in aged 'lupus mice' (MRL-lpr/lpr and NZB x NZW F1) both lead to increased C3 mRNA expression in whole kidney. In situ hybridization was used to determine the intrarenal cell type(s) capable of constitutive and regulated C3 mRNA expression. Normal mice injected with Escherichia coli LPS show a marked increase in whole kidney C3 mRNA over control (saline-injected) animals. The renal C3 mRNA in LPS-stimulated mice was found in cortical tubular epithelium. By contrast, in aged (18 week) MRL-lpr/lpr mice, which develop lupus nephritis, the increased intrarenal C3 messenger RNA was localized to perivascular inflammatory cells surrounding medium-sized arteries. Similar perivascular infiltrates were seen in the lungs of the MRL-lpr/lpr mice, and focal inflammatory cell infiltrates were also found in the myocardium. Leucocytes in these infiltrates accounted for the increased C3 expression in these tissues. These findings suggest cell as well as tissue specificity of the response to inflammatory stimuli in the local extrahepatic production of the third component of complement.