INHIBITION BY BACTERIAL LIPOPOLYSACCHARIDE OF SPONTANEOUS AND TNF-ALPHA-INDUCED HUMAN NEUTROPHIL APOPTOSIS IN-VITRO

In the previous paper (Takeda et al, Int. Immunol., 5, 691-694, 1993), we demonstrated that tumor necrosis factor-alpha (TNF-alpha) promptly accelerates apoptosis of human neutrophils in vitro. In order to dete rmine the role of neutrophil apoptosis in defending against bacterial infection, we studied the effect of bacterial lipopolysaccharide (LPS) on this process. LPS inhibited spontaneous and TNF-alpha-induced huma n neutrophil apoptosis in vitro, as determined by 1) light and electro n microscopy, 2) flow cytometry, and 3) agarose gel electrophoresis of DNA. Low concentrations of cycloheximide, a protein synthesis inhibit or, which alone did not affect neutrophil apoptosis, were able to redu ce spontaneous apoptosis inhibition by LPS, suggesting the involvement of newly synthesized protein in this phenomenon.