title: Human skin mast cells rapidly release preformed and newly generated TNF-alpha and IL-8 following stimulation with anti-IgE and other secretagogues.
abstract: Several groups have previously reported that rodent or human leukemic mast cells produce inflammatory cytokines such as TNF-alpha and IL-8 as well as the pro-allergic cytokines IL-4, IL-5 and IL-13. Comparatively little is known, however, regarding the ability of normal human skin mast cells to secrete these factors following either IgE-dependent or IgE-independent modes of activation. We therefore investigated whether normal human skin mast cells produce these cytokines following stimulation by a variety of secretagogues. Enriched isolated skin mast cells released both TNF-alpha and IL-8 following activation with either anti-IgE, SCF, substance P, compound 48/80 or A23187. This release was dose- and time-dependent, with maximal levels being reached within 4 h of stimulation involving, in part, the secretion of preformed stores of both cytokines. In accordance with this, using lysates of highly purified (>90%) skin mast cells, we could demonstrate that both TNF-alpha and IL-8 mRNA and protein were present in both unstimulated as well as stimulated mast cells. In stark contrast to these results, no significant levels of either IL-4, IL-5 or IL-13 were detected, regardless of the secretagogue used or the period of stimulation. These results show that human skin mast cells are capable of rapidly secreting pro-inflammatory cytokines like TNF-alpha and IL-8 following IgE-dependent activation and stimulation by the neuropeptide substance P, SCF and the basic polypeptide analogue compound 48/80. In contrast to other types of human mast cells however, human skin mast cells were incapable of secreting IL-4, IL-5 or IL-13 in these settings.
authors.affiliation: Department of Dermatology, Medical University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: B F
authors.initials: BF
authors.lastname: Gibbs
authors.forename: J
authors.initials: J
authors.lastname: Wierecky
authors.forename: P
authors.initials: P
authors.lastname: Welker
authors.forename: B M
authors.initials: BM
authors.lastname: Henz
authors.forename: H H
authors.initials: HH
authors.lastname: Wolff
authors.forename: J
authors.initials: J
authors.lastname: Grabbe
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D016209:Interleukin-8 / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019089:Stem Cell Factor / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D016209:Interleukin-8; D007476:Ionophores; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D007073:Immunoglobulin E; D000001:Calcimycin; D003189:p-Methoxy-N-methylphenethylamine