Immunostimulatory Effects of Platinum Compounds: Correlation between Sensitizing Properties in vivo and Modulation of Receptor-Mediated Endocytosis in vitro

Abstract

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 inert. 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.

Effect of two complex platinum salts on human sperm motility and acrosome reaction

“…The worldwide production and industrial use of platinum (Pt) and its compounds have dramatically increased since the introduction of Pt‐containing automobile catalysts two decades ago ( Rosner & Merget, 1990; WHO, 1991; Schuppe et al ., 1997 ). Apart from its applications due to excellent catalytic properties, Pt is utilized in jewellery, dental alloys, thermoelectrical devices and glass industries ( WHO, 1991).…”

“…However, the molecular mechanism underlying this exocytic process has not been studied. As far as sensitizing properties are concerned, a structure–activity relationship between different complex Pt salts was defined both in vitro and in vivo in a murine model ( Schuppe et al ., 1997 ). Therefore, two structurally and chemically different Pt compounds—sodium‐hexachloroplatinate‐(IV), Na 2 [PtCl 6 ], known as potent sensitizer, and the nonimmunogenic tetraamineplatinum‐(II)‐chloride, [Pt(NH 3 ) 4 ]Cl 2 — were selected for the experiments.…”

Platinum in the environment: frequency of reactions to platinum‐group elements in patients with dermatitis and urticaria

“…Some of these salts showed strong sensitizing potency in animal models. Schuppe et al demonstrated, by means of the popliteal lymph node assay in mice, that hexa and tetrachloroplatinates had the highest sensitizing potency (4).…”

Interleukin-1β and surface marker expression changes induced by tetrachloroplatinate in human monocyte-derived dendritic cells

“…The symptoms include skin changes (urticaria, contact dermatitis) and respiratory disorders ranging from sneezing, shortness of breath, and cyanosis to severe asthma [2][3][4][5][6]. The sensitizing properties of different platinum salts (e.g., disodium or ammonium hexachloroplatinate) were also proved in mice by means of the Popliteal Lymph Node Assay [3,7] and the Local Lymph Node Assay [8].…”