LIPOPOLYSACCHARIDE STIMULATES PHOSPHORYLATION OF EUKARYOTIC INITIATION FACTOR-4F IN MACROPHAGES AND TUMOR-NECROSIS-FACTOR PARTICIPATES IN THIS EVENT

Bacterial lipopolysaccharide (LPS) produces rapid changes in macrophag e protein synthesis and function. Phosphorylation of the 25 kDa mRNA c ap-binding protein (eIF-4E) in model systems regulates the efficiency of protein synthesis. We report that both LPS and tumor necrosis facto r-alpha (TNF-alpha) stimulate phosphorylation of eIF-4E and the p220 c omponent of eIF-4F in bone marrow-derived macrophages. Moreover, anti- TNF-alpha antibodies inhibit LPS-stimulated phosphorylation of eIF-4E and p220 by 43% (+/- 6%) and 50% (+/- 5%), respectively. Our results i ndicate that LPS stimulates eIF-4F phosphorylation by a TNF-alpha-depe ndent mechanism, and suggest that phosphorylation of eIF-4F might play a role in the post-transcriptional regulation of gene expression in m acrophages exposed to LPS.