Cell type- and developmental stage-specific activation of NF-kappaB 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-kappaB (NF-kappaB), 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 kappaB binding activity that was receptor-dependent and involved the p50 and p65 subunits of the NF-kappaB/Rel family of proteins. The activation of NF-kappaB by fMLF appeared to be cell-specific and different from the activation of NF-kappaB by tumor necrosis factor-alpha (TNFalpha). Neutrophil preparations that responded to fMLF, TNFalpha, and lipopolysaccharides with interleukin-8 secretion did not show NF-kappaB activation, whereas N-formyl peptide receptor (FPR)-transfected HL-60 cells were responsive to TNFalpha but not fMLF for NF-kappaB activation. Differentiation of FPR-transfected HL-60 cells with dimethyl sulfoxide for 3-5 days conferred the capability of the cells to activate NF-kappaB in response to fMLF without a significant increase in the amount of FPR. These results identify NF-kappaB 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.
Browning
D D
DD
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Pan
Z K
ZK
Prossnitz
E R
ER
Ye
R D
RD
D002478:Cells, Cultured; D018922:HL-60 Cells; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction
D016328:NF-kappa B; D009240:N-Formylmethionine Leucyl-Phenylalanine