Immunostimulatory effects of platinum compounds: correlation between sensitizing properties in vivo and modulation of receptor-mediated endocytosis in vitro.
The sensitizing properties of different complex salts of platinum were defined in vivo by means of the popliteal lymph node (PLN) assay in mice. Hexa- and tetrachloroplatinates were confirmed to be highly immunogenic, inducing vigorous primary immune responses in the draining PLN following single subcutaneous injections. Flow-cytometric analysis revealed a dramatic increase in the total number of cells expressing proliferating cell nuclear antigen. The majority of these cells were of the T helper phenotype (CD4+) reflecting the T-cell dependence of the PLN response induced by Pt salts such as Na2[PtCl6] or Na2[PtCl4]. In contrast, [Pt(NH3)4]Cl2 failed to elicit a significant increase in PLN cell proliferation when compared with saline-treated controls. The differential immunogenicity of the Pt compounds found in vivo directly correlated with their capacity to modulate mechanisms of receptor-mediated endocytosis in murine Langerhans cells in vitro. The reactivity of Na2[PtCl6] or Na2[PtCl4] resembled that of potent contact sensitizers in this endocytosis assay whereas [Pt(NH3)4]Cl2 proved to be mert. These results suggest that [Pt(NH3)4]Cl2 might be less harmful to humans than hexa- or tetrachloroplatinates. As demonstrated with Pt compounds, monitoring of direct effects of low-molecular-weight chemicals on antigen-presenting dendritic cells in vitro is able to predict their sensitizing potential in vivo.
Schuppe
H C
HC
Department of Dermatology, Heinrich Heine University, Düsseldorf, Germany.
Kulig
J
J
Kühn
U
U
Lempertz
U
U
Kind
P
P
Knop
J
J
Becker
D
D
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002712:Chlorides / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity; D002945:Cisplatin / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity; D009783:Dermatitis, Occupational / Q000209:etiology; D004705:Endocytosis / Q000187:drug effects*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000209:etiology; D007159:Immunologic Tests; D066298:In Vitro Techniques; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D017671:Platinum Compounds / Q000276:immunology / Q000494:pharmacology* / Q000633:toxicity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D002712:Chlorides; D017671:Platinum Compounds; C036919:tetrachloroplatinate; D002945:Cisplatin; C038762:disodium hexachloroplatinate