Tumor necrosis factor and endotoxin can cause neutrophil activation through separate pathways.
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.
Moore
F D
FD
Department of Surgery, Harvard Medical School, Brigham and Women's Hospital, Boston, Mass.
Socher
S H
SH
Davis
C
C
D000906:Antibodies / Q000502:physiology; D003179:Complement C3b / Q000032:analysis; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005455:Fluorescent Antibody Technique; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D011951:Receptors, Complement / Q000032:analysis / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000906:Antibodies; D004731:Endotoxins; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D011951:Receptors, Complement; D014409:Tumor Necrosis Factor-alpha; D003179:Complement C3b