Recombinant human cytokines stimulate neutrophil adherence to IgG autoantibody-treated epithelial basement membranes.
We investigated the ability of the purified recombinant human cytokines: tumor necrosis factor-alpha (rTNF), granulocyte-macrophage colony-stimulating factor (rGM-CSF), interleukin-1 beta (rIL-1), interleukin-3, and tumor necrosis factor-beta (rTNF-beta) to stimulate neutrophil adherence (NA) to basement membranes (BMs) of stratified squamous epithelia pretreated with autoantibodies (ABM) specific for the BM matrix protein, type-VII collagen. rTNF, rGM-CSF, rIL-1, and rTNF-beta, but not IL-3, stimulated NA and stimulation was ABM- and cytokine-concentration-dependent. Stimulation was cytokine-specific and not due to endotoxin since it was significantly inhibited by cytokine-specific antibodies but not by polymyxin B (PB). rTNF and rGM-CSF were the most potent stimulators, were effective at concentrations less than 0.067 ng/ml, and stimulated NA greater than 600%. Relative potency was: rTNF = rGM-CSF greater than rTNF-beta greater than rIL-1. Stimulation by rTNF was due to a rapid, time-dependent effect on the neutrophil, and NA appeared to be dependent, in part, on the low-affinity neutrophil receptor for IgG, Fc(gamma)RIII, because it could be specifically inhibited by monoclonal antibody (3G8) to Fc(gamma)RIII. These results suggest that rTNF, rGM-CSF, rIL-1, and rTNF-beta may contribute individually or in combination to immune-mediated inflammation and tissue injury by stimulating immune adherence of neutrophils to tissue-bound autoantibodies and immune complexes.
Department of Dermatology, University of North Carolina School of Medicine, Chapel Hill 27599.
W R
WR
Gammon
J D
JD
Hendrix
K
K
Mangum
E W
EW
Jeffes
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001485:Basement Membrane / Q000276:immunology / Q000502:physiology; D001685:Biological Factors / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D016207:Cytokines; D004848:Epithelium / Q000276:immunology / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007375:Interleukin-1 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000276:immunology; D012879:Skin Physiological Phenomena; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001685:Biological Factors; D003115:Colony-Stimulating Factors; D016207:Cytokines; D006133:Growth Substances; D007074:Immunoglobulin G; D007375:Interleukin-1; D007377:Interleukin-3; D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor