Tumor necrosis factor-alpha dependent cytotoxicity of human skin mast cells is enhanced by anti-IgE antibodies.
Mast cells dispersed from human skin and purified by density-gradient centrifugation were cytotoxic toward the mouse fibrosarcoma cell line WEHI-164. Skin mast cells were not cytotoxic toward the NK cell-sensitive cell line K562. Killing of WEHI-164 occurred over a prolonged (greater than 18 h) period of incubation with mast cells and was effectively inhibited by polyclonal antibodies and mAb against TNF-alpha suggesting that this cytokine plays an important role in mast cell-mediated cytotoxicity. Whereas lysates of rat peritoneal mast cells exhibited cytotoxicity toward WEHI-164, this was not found with lysates of unstimulated skin mast cells suggesting that TNF-alpha is not stored preformed in the latter. Killing of WEHI-164 cells by skin mast cells was enhanced by anti-IgE and there was a significant correlation between histamine release and cytotoxicity after activation with this stimulus. We conclude that human skin mast cells are a potential source of TNF-alpha and suggest that these cells, particularly after activation, might contribute to the synthesis of this multifunctional cytokine in inflammatory sites.
Benyon
R C
RC
Immunological Sciences Research Group, Microbiology and Infectious Diseases, University of Calgary Health Sciences, Alberta, Canada.
Bissonnette
E Y
EY
Befus
A D
AD
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D003513:Cycloheximide / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000166:cytology / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000888:Antibodies, Anti-Idiotypic; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D003513:Cycloheximide