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.
Immunological Sciences Research Group, Microbiology and Infectious Diseases, University of Calgary Health Sciences, Alberta, Canada.
R C
RC
Benyon
E Y
EY
Bissonnette
A D
AD
Befus
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