Journal Article

Divergent Effect of Cobalt and Beryllium Salts on the Fate of Peripheral Blood Monocytes and T Lymphocytes

Fabiana Paladini, Elisa Cocco, Ilaria Potolicchio, Henrieta Fazekasova, Giovanna Lombardi, Maria Teresa Fiorillo and Rosa Sorrentino

in Toxicological Sciences

Volume 119, issue 2, pages 257-269
Published in print February 2011 | ISSN: 1096-6080
Published online October 2010 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfq328
Divergent Effect of Cobalt and Beryllium Salts on the Fate of Peripheral Blood Monocytes and T Lymphocytes

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Occupational exposure to metals such as cobalt and beryllium represents a risk factor for respiratory health and can cause immune-mediated diseases. However, the way they act may be different. We show here that the two metals have a divergent effect on peripheral T lymphocytes and monocytes: BeSO4 induces cell death in monocytes but not in T lymphocytes, which instead respond by producing Interferon gamma (IFN-γ); conversely, CoCl2 induces apoptosis in T lymphocytes but not in monocytes. Interestingly, both metals induce p53 overexpression but with a dramatic different outcome. This is because the effect of p53 in CoCl2-treated monocytes is counteracted by the antiapoptotic activity of cytoplasmic p21Cip1/WAF1, the activation of nuclear factor κB, and the inflammasome danger signaling pathway leading to the production of proinflammatory cytokines. However, CoCl2-treated monocytes do not fully differentiate into macrophage or dendritic cells, as inferred by the lack of expression of CD16 and CD83, respectively. Furthermore, the expression of HLA-class II molecules, as well as the capability of capturing and presenting the antigens, decreased with time. In conclusion, cobalt keeps monocytes in a partially activated, proinflammatory state that can contribute to some of the pathologies associated with the exposure to this metal.

Keywords: monocytes; lymphocytes; metal salts; lung; inflammation; inflammasome

Journal Article.  7054 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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