IgG-coated erythrocytes augment LPS-stimulated TNF-alpha secretion, TNF-alpha mRNA levels, and TNF-alpha mRNA stability in macrophages

Previous studies have shown that IgG-coated erythrocytes (EIgG) augment the LPS-stimulated increase in serum TNF-alpha levels in animals and the LPS-s timulated secretion of TNF-alpha by isolated macrophages. The present study evaluated the mechanism for the effect of EIgG on LPS-stimulated TNF-alpha secretion in the murine macrophage cell Line, RAN 264.7, Incubation of the macrophages with EIgG or IgG-coated glass beads caused a dose-dependent au gmentation of LPS-stimulated TNF-alpha secretion. The addition of EIgG incr eased the rate of LPS-stimulated TNF-alpha protein secretion between 2 and 4 hr after LPS. Accordingly, EIgG increased the levels of TNF-alpha mRNA at 2 and 3 hr after LPS. The increase in the LPS-stimulated TNF-alpha mRNA le vels caused by EIgG was associated with an increase in TNF-alpha mRNA stabi lity. Thus, the augmentation of LPS-stimulated TNF-alpha secretion by EIgG was associated with an increase in TNF-alpha mRNA levels which at least par tly resulted from an increase in the stability of TNF-alpha mRNA. (C) 2000 Academic Press.