Cell type and developmental stage-specific activation of NF-kappa B by fMet-Leu-Phe in myeloid cells

Chemoattractants induce a variety of phagocytic functions including transendothelial migration, degranulation, and the generation of superoxide anions, We report here that the prototypic chemotactic peptide fMet-Leu-Phe (fMLF) stimulates the activation of nuclear factor-kappa B (NF-kappa B), a transcription factor that is central to the regulation of proinflammatory immediate-early gene expression, In freshly prepared peripheral blood mononuclear cells, fMLF (1-100 nM) induced a kappa B binding activity that was receptor-dependent and involved the p50 and p65 subunits of the NF-kappa B/Rel family of proteins, The activation of NF-kappa B by fMLF appeared to be cell-specific and different from the activation of NF-kappa B by tumor necrosis factor alpha (TNF alpha). Neutrophil preparations that responded to fMLF, TNF alpha, and lipopolysaccharides with interleukin-8 secretion did not show NF-kappa B activation, whereas N-formyl peptide receptor (FPR)-transfected HL-60 cells were responsive to TNF alpha but not fMLF for NF-kappa B activation, Differentiation of FPR-transfected HL-60 cells with dimethyl sulfoxide for 3-5 days conferred the capability of the cells to activate NF-kappa B in response to fMLF without a significant increase in the amount of FPR, These results identify NF-kappa B as a transcription factor that can be activated by the prototypic chemotactic peptide and demonstrate that this function is both highly regulated and dependent on signaling components specifically expressed during myeloid differentiation.