Tumor necrosis factor and endotoxin can cause neutrophil activation through separate pathways
F. D. Moore Jr, S. H. Socher and C. Davis
Department of Surgery, Harvard Medical School, Brigham and Women's Hospital, Boston, Mass.
We investigated the possibility that tumor necrosis factor (TNF) mediates
neutrophil activation by endotoxin. The number of C3b receptors on the
neutrophil cell-surface was used as the indicator of activation, as
assessed by indirect immunofluorescence. Incubation of buffy-coat
neutrophils with TNF-alpha for 30 minutes at 37 degrees C caused neutrophil
activation, increasing C3b receptor-dependent fluorescence from 340 with
buffer alone to 580 with TNF (250 pg/mL). Increasing amounts of anti-TNF
IgG progressively inhibited neutrophil activation by TNF (250 pg/mL).
Addition of the active dose range of anti-TNF to neutrophils incubating in
endotoxin (10 ng/mL) did not affect the degree of endotoxin-mediated
neutrophil activation. Mixtures of neutrophils with the 50% suppressive
dose of anti-TNF and varying endotoxin concentrations showed the same
degree of neutrophil activation as mixtures without the antibody. Thus, an
antibody that can inhibit TNF-mediated neutrophil activation does not
inhibit endotoxin-mediated neutrophil activation. We conclude that
endotoxin and TNF can activate neutrophils through separate pathways.
