SODIUM-BUTYRATE DELAYS NEUTROPHIL APOPTOSIS - ROLE OF PROTEIN-BIOSYNTHESIS IN NEUTROPHIL SURVIVAL

Sodium butyrate, which directly affects chromatin structure and functi on in many cells, is as effective as granulocyte-macrophage colony-sti mulating factor (GM-CSF) in delaying apoptosis in human neutrophils. B oth butyrate and GM-CSF preserved the ability of neutrophils cultured for 22 h in vitro to generate reactive oxidants and express receptors such as CD16, They also delayed apoptotic morphology and DNA fragmenta tion, and stimulated de novo biosynthesis: newly-labelled polypeptides detected by 2D-polyacrylamide gel electrophoresis after treatment wit h GMCSF and butyrate were very similar. Cycloheximide abrogated the ef fects of both GM-CSF and butyrate. Exposure to butyrate for Ih did not prime oxidant production and did not up-regulate expression of CD11b. Hence, unlike GM-CSF, butyrate does not stimulate translocation of gr anules to the plasma membrane, These data suggest that active gene exp ression is involved in the regulation of neutrophil apoptosis and chan ges in chromatin structure and function may control apoptosis in these cells.