CELLULAR SPECIFICITY OF MURINE RENAL C3 EXPRESSION IN 2 MODELS OF INFLAMMATION

The expression of the complement protein C3 in extrahepatic tissues is highly regulated during the course of inflammation. Hence, systemic a cute phase stimuli such as bacterial lipopolysaccharide (LPS) and auto immune nephritis in aged 'lupus mice' (MRL-lpr/lpr and NZB x NZW F-1) both lead to increased C3 mRNA expression in whole kidney. In situ hyb ridization was used to determine the intrarenal cell type(s) capable o f constitutive and regulated C3 mRNA expression. Normal mice injected with Escherichia coli LPS show a marked increase in whole kidney C3 mR NA over control (saline-injected) animals. The renal C3 mRNA in LPS-st imulated mice was found in cortical tubular epithelium. By contrast, i n aged (18 week) MRL-lpr/lpr mice, which develop lupus nephritis, the increased intrarenal C3 messenger RNA was localized to perivascular in flammatory cells surrounding medium-sized arteries. Similar perivascul ar infiltrates were seen in the lungs of the MRL-lpr/lpr mice, and foc al inflammatory cell infiltrates were also found in the myocardium. Le ucocytes in these infiltrates accounted for the increased C3 expressio n in these tissues. These findings suggest cell as well as tissue spec ificity of the response to inflammatory stimuli in the local extrahepa tic production of the third component of complement.