title: Tumor necrosis factor and endotoxin can cause neutrophil activation through separate pathways.
abstract: 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.
authors.affiliation: Department of Surgery, Harvard Medical School, Brigham and Women's Hospital, Boston, Mass.
authors.forename: F D
authors.initials: FD
authors.lastname: Moore
authors.forename: S H
authors.initials: SH
authors.lastname: Socher
authors.forename: C
authors.initials: C
authors.lastname: Davis
mesh_terms: 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*
chemical_list: D000906:Antibodies; D004731:Endotoxins; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D011951:Receptors, Complement; D014409:Tumor Necrosis Factor-alpha; D003179:Complement C3b