The complement factors I (FI) and H (FH) are complement regulatory proteins. FI, a
highly glycosylated serine protease of 88 kDa cleaves the alpha-chains of both complement
components C3b and C4b, thereby inactivating them. Complement FH, a glycoprotein of
150 kDa which is composed of 20 short consensus repeats synergizes with FI by increasing
the affinity of FI for C3b in the C3b/FH complex by about 15-fold as compared to free
C3b. Furthermore, FH prevents factor B from binding to C3b and promotes the dissociation
of the C3bBb complex. Both, FI and FH are mainly synthesized in the liver. According
to the quantification of specific mRNA of both factors, various amounts are produced
by different liver cell types, i.e. hepatocytes (HC) and Kupffer cells (KC). Investigations
of cultured primary HC and KC from rat liver showed that FI is exclusively synthesized
and secreted by HC whereas FH is synthesized by both HC and KC. Using quantitative-competitive
PCR for the quantification of FH-specific mRNA, its constitutive rate of synthesis
was found to be nearly ten times higher in KC than in HC. An extrahepatic source of
both proteins are human umbilical vein endothelial cells (HUVEC) in which the synthesis
of FI is upregulated by IL-6 which is in accord with the upregulation observed in
rat HC and two rat hepatoma cell lines (FAO and H4IIE). Three other proinflammatory
cytokines, IL-1beta, IFN-gamma and TNF-alpha, were alone or in combination, without
any effect on the regulation of FI. This demonstrates that the regulation of FI is
similar in HUVEC and HC. These results are in contrast to a previously described IFN-gamma-mediated
upregulation of FI in HUVEC and suggest, in accordance with other investigations on
extrahepatic sources of FI (e.g. myoblasts), that IFN-gamma has probably no prominent
role in the regulation of FI. Instead, IL-6 appears to be the main upregulating cytokine
of FI mRNA and of FI protein synthesis in HC as well as in rat and human hepatoma
cells and in HUVEC. Of note are experiments by others and us who could not identify
FI-specific mRNA in peripheral blood-derived monocytes, granulocytes, or B- and T-cells
of man or rat and in rat peritoneal macrophages. FI-specific mRNA could also not be
detected in B- or T-cell lymphoma cells, whereas FH-specific mRNA was easily detectable
in both human and rat monocytes, and in rat peritoneal macrophages. These data support
the notion that FI in contrast to FH is not expressed by cells of the monocyte-macrophage
lineage or by other leukocytes of peripheral blood, at least in the absence of additional
stimulants.