Hepatic parenchymal cells respond in many different ways to acute-phase
cytokines. Some responses may protect against damage by liver-derived inflammatory mediators. Previous investigations have shown that
cytokines cause increased secretion by
hepatoma cells of soluble
complement regulatory
proteins, perhaps providing protection from
complement attack. More important to cell protection are the membrane
complement regulators. Here we examine, using flow cytometry and Northern blotting, the effects of different
cytokines, singly or in combination, on expression of membrane-bound
complement regulators by a
hepatoma cell line. The combination of tumour
necrosis factor-alpha, IL-1beta, and
IL-6 caused increased expression of CD55 (three-fold) and CD59 (two-fold) and decreased expression of CD46 at day 3 post-exposure.
Interferon-gamma reduced expression of CD59 and strongly antagonized the up-regulatory effects on CD59 mediated by the other
cytokines.
Complement attack on antibody-sensitized
hepatoma cells following a 3-day incubation with the optimum combination of acute-phase
cytokines revealed increased resistance to
complement-mediated lysis and decreased C3b deposition. During the
acute-phase response there is an increased hepatic synthesis of the majority of
complement effector
proteins. Simultaneous up-regulation of expression of CD55 and CD59 may serve to protect hepatocytes from high local concentrations of
complement generated during the
acute-phase response.