title: Simple chemicals can induce maturation and apoptosis of dendritic cells.
abstract: As is well known in the case of Langerhans cells, dendritic cells (DCs) play a crucial role in the initiation of immunity to simple chemicals such as noted in the contact hypersensitivity. Because DCs are scattered in non-lymphoid organs as immature cells, they must be activated to initiate primary antigen-specific immune reactions. Therefore, we hypothesized that some simple chemicals must affect the function of DCs. In this paper, we first demonstrated that human monocyte-derived DCs responded to such simple chemicals as 2, 4-dinitrochlorobenzene (DNCB), 2,4,6-trinitrochlorobenzene (TNCB), 2, 4-dinitrofluorobenzene (DNFB), NiCl2, MnCl2, CoCl2, SnCl2, and CdSO4 by augmenting their expression of CD86 or human leucocyte antigen-DR (HLA-DR), down-regulating c-Fms expression or increasing their production of tumour necrosis factor-alpha (TNF-alpha). In addition, the DCs stimulated with the chemicals demonstrated increased allogeneic T-cell stimulatory function. Next, we found that, among these chemicals, only NiCl2 and CoCl2 induced apoptosis in them. Finally, we examined the effects of these chemicals on CD86 expression by three different macrophage subsets and DCs induced from the cultures of human peripheral blood monocytes in the presence of macrophage colony-stimulating factor (M-CSF), M-CSF + interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), and GM-CSF + IL-4, respectively. Among them, only DCs dramatically augmented their expression of CD86. These observations have revealed unique characteristics of DCs, which convert chemical stimuli to augmentation of their antigen presenting function, although their responses to different chemicals were not necessarily uniform in the phenotypic changes, cytokine production or in the induction of apoptosis.
authors.affiliation: Department of Dermatology, Tohoku University School of Medicine, Aobaku, Sendai, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Manome
authors.forename: S
authors.initials: S
authors.lastname: Aiba
authors.forename: H
authors.initials: H
authors.lastname: Tagami
mesh_terms: D015703:Antigens, CD / Q000276:immunology*; D016587:Antimutagenic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051940:B7-2 Antigen; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015870:Gene Expression; D016236:Genes, fms; D006684:HLA-DR Antigens / Q000276:immunology*; D006241:Haptens / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D015636:Magnesium Chloride / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology*; D008670:Metals / Q000494:pharmacology*; D009532:Nickel / Q000494:pharmacology; D010853:Picryl Chloride / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D017967:Zinc Compounds / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D016587:Antimutagenic Agents; D051940:B7-2 Antigen; D015415:Biomarkers; C497964:CD86 protein, human; D002712:Chlorides; D006684:HLA-DR Antigens; D006241:Haptens; D008562:Membrane Glycoproteins; D008670:Metals; D014409:Tumor Necrosis Factor-alpha; D017967:Zinc Compounds; D015636:Magnesium Chloride; D003035:Cobalt; C022838:nickel chloride; D003300:Copper; D009532:Nickel; C016837:zinc chloride; C028419:cuprous chloride; C018021:cobaltous chloride; D010853:Picryl Chloride