The subcomponent of complement C1, C1q, mediates complement activation via the classical pathway, and therefore may play an important role in the inflammatory processes in which complement activation is involved. The aim of our study was to investigate C1q synthesis by macrophages of normal and of acutely damaged livers. The localization of C1q in liver tissue was studied by immunohistochemistry. Rat liver tissue macrophages were isolated from normal as well as from acutely damaged (carbon tetrachloride model) liver, and were separated into small, monocyte-like phagocytes and large, mature tissue macrophages, as revealed by immunocytochemistry. C1q gene expression was studied by endogeneous labeling of newly synthesized proteins, immunoprecipitation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and by reverse-transcription polymerase chain reaction (RT-PCR) of C1qB messenger RNA (mRNA). Semiquantitative analysis was performed by Northern blotting of total RNA and hybridization with the radioactively labeled RT-PCR product. C1 esterase inhibitor synthesis was studied in parallel. For comparison, C1q and C1-inhibitor synthesis were also investigated in blood monocytes and peritoneal macrophages. C1q was weakly detectable in sinusoidal cells of the normal liver. C1qB mRNA, as well as constitutive synthesis and secretion of C1q, was clearly detected in freshly isolated and cultured Kupffer cells from normal rat liver. In comparison, newly recruited “inflammatory” macrophages from damaged rat liver synthesized considerably lower amounts of the protein, similar to what was found in the monocyte-like macrophages of normal liver and in peritoneal macrophages. Monocyte C1qB mRNA was not detected even by RT- PCR, and remained undetectable during the time in culture. Similar behavior was observed for C1-inhibitor synthesis. Treatment of the cultures with interferon gamma (IFN-γ) or lipopolysaccharide (LPS) strongly decreased, whereas treatment with dexamethasone strongly increased C1q gene expression in the macrophage populations, and induced C1qB mRNA in cultured monocytes, as revealed by RT-PCR. Kupffer cells of normal liver may produce considerable amounts of C1q, whereas the inflammatory macrophages of the acutely damaged liver may not be so important for the synthesis of C1q.
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