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J. Biol. Chem., Vol. 265, Issue 33, 20241-20246, 11, 1990
MA Cassatella, F Bazzoni, RM Flynn, S Dusi, G Trinchieri and F Rossi
In this study, we analyzed the expression of genes encoding for components
of the phagocyte superoxide anion-generating system in human phagocytes
treated with interferon-gamma (IFN-gamma) or lipopolysaccharide (LPS).
Human neutrophils express high levels of the 47-kDa cytosolic factor
(p47-phox), which are down-regulated after treatment with IFN-gamma, but
not with LPS. On the contrary, the steady- state levels of the heavy chain
subunit of cytochrome b558 (gp91-phox) were increased by IFN-gamma and LPS
in human monocyte-derived macrophages and neutrophils in a time- and
dose-dependent fashion, whereas cytochrome b558 light chain subunit
(p22-phox) mRNA was not influenced by either agent. Studies on
post-transcriptional regulation at the level of mRNA stability indicate
that, in neutrophils, IFN-gamma has no influence on gp91-phox and p47-phox
mRNA half-lives. The content of the two cytochrome b558 subunits was
quantified by enzyme-linked immunosorbent assay, which revealed that, in
neutrophils, gp91-phox levels doubled after 4 h of treatment with IFN-gamma
or LPS. Monocyte/macrophage maturation was associated with a gradual
decrease in gp91-phox mRNA and protein levels, which were both restored by
treatment with IFN-gamma for 24-48 h. These results suggest that induction
of the gp91-phox gene and protein product by IFN-gamma or LPS is an
important requirement in the mechanism of the enhancement of neutrophil and
macrophage oxidative metabolism.
Molecular basis of interferon-gamma and lipopolysaccharide enhancement of phagocyte respiratory burst capability. Studies on the gene expression of several NADPH oxidase components
Institute of General Pathology, University of Verona, Italy.
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