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The Ruthenium Complex cis-(Dichloro)Tetraammineruthenium(III) Chloride Presents Immune Stimulatory Activity on Human Peripheral Blood Mononuclear Cells

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Abstract

Ruthenium compounds in general are well suited for medicinal applications. They have been investigated as immunosuppressants, nitric oxide scavengers, antimicrobial agents, and antimalarials. The aim of this study is to evaluate the immunomodulatory activity of cis-(dichloro)tetraammineruthenium(III) chloride (cis-[RuCl2(NH3)4]Cl) on human peripheral blood mononuclear cells (PBMC). The cytotoxic studies performed here revealed that the ruthenium(III) complex presents a cytotoxic activity towards normal human PBMC, only at very high concentration. Results also showed that cis-[RuCl2(NH3)4]Cl presents a dual role on PBMC stimulating proliferation and interleukin-2 (IL-2) production at low concentration and inducing cytotoxicity, inability to proliferate, and inhibiting IL-2 production at high concentration. The noncytotoxic activity of cis-[RuCl2(NH3)4]Cl at low concentration towards PBMC, which correlates with the small number of annexin V positive cells and also the absence of DNA fragmentation, suggest that this compound does not induce apoptosis on PBMC. For the first time, we show that, at low concentration (10–100 µg L−1), the cis-[RuCl2(NH3)4]Cl compound induces peripheral blood lymphocytes proliferation and also stimulates them to IL-2 production. These results open a new potential applicability of ruthenium(III) complexes as a possible immune regulatory compound acting as immune suppressor at high concentration and as immune stimulator at low concentration.

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Abbreviations

cis-[RuCl2(NH3)4]Cl:

cis-(dichloro)tetraammineruthenium(III) chloride

DMSO:

dimethyl sulfoxide

EDTA:

ethylenediaminetetraacetic acid

ELISA:

enzyme-linked immunosorbent assay

FACS:

fluorescence-activated cell sorter

FITC:

fluorescein isothiocyanate

HEPES:

4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid

IC50 :

50% inhibitory concentration

IL-2:

interleukin-2

Jurkat:

human T cell leukemia cell line

LPS:

(bacterial) lipopolysaccharide

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NAMI-A:

imidazolium-trans-DMSO-imidazole-tetrachlororuthenate

PBMCs:

peripheral blood mononuclear cells

PHA:

phytohemagglutinin

PI:

propidium iodide

RPMI:

Roswell Park Memorial Institute medium

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Acknowledgments

This work was supported the Research and Projects Financing (FINEP; grant no. 01.06.0941.00/CT-Saúde to Elisângela de Paula Silveira-Lacerda), the Foundation for the Support of Research in the State of São Paulo (FAPESP), and the Brazilian National Counsel of Technological and Scientific Development (CNPq) through fellowships to Cesar Augusto Sam Tiago Vilanova-Costa (grant no. 381303/2007-1) and Flávia de Castro Pereira (grant no. 381302/2007-5).

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Authors and Affiliations

  1. Laboratório de Genética Molecular e Citogenética, Instituto de Ciências Biológicas (ICB I), Universidade Federal de Goiás (UFG), Sala 200, Campus Samambaia (Campus II), Cx. Postal: 131, Goiânia, Goiás, Brazil

    Elisângela de Paula Silveira-Lacerda, Cesar Augusto Sam Tiago Vilanova-Costa & Flávia de Castro Pereira

  2. Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia (UFU), Uberlândia, Minas Gerais, Brazil

    Amélia Hamaguchi, Luiz Ricardo Goulart & Maria Inês Homsi-Brandenburgo

  3. Instituto de Química, Universidade Federal de Uberlândia (UFU), Uberlândia, Minas Gerais, Brazil

    Luiz Alfredo Pavanin

  4. Faculdade Patos de Minas (FPM), Patos de Minas, Minas Gerais, Brazil

    Wagner Batista dos Santos

  5. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil

    Andreimar Martins Soares & Auro Nomizo

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  1. Elisângela de Paula Silveira-Lacerda
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  2. Cesar Augusto Sam Tiago Vilanova-Costa
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Correspondence to Elisângela de Paula Silveira-Lacerda.

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Silveira-Lacerda, E.P., Vilanova-Costa, C.A.S.T., Pereira, F.C. et al. The Ruthenium Complex cis-(Dichloro)Tetraammineruthenium(III) Chloride Presents Immune Stimulatory Activity on Human Peripheral Blood Mononuclear Cells. Biol Trace Elem Res 133, 270–283 (2010). https://doi.org/10.1007/s12011-009-8440-8

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