Divergent effect of Cobalt and Beryllium salts on the fate of peripheral blood monocytes and T lymphocytes.

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Paladini, F. | Cocco, E. | Potolicchio, Ilaria | Henrieta, Fazkasova | Giovanna, Lombardi | Fiorillo, Mt | Sorrentino, R.

Edité par CCSD -

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; conversely CoCl2 induces apoptosisin T lymphocytes but not in monocytes. Interestingly, both metals induce p53 over-expression, 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 NF-kB and the inflammasome danger signalling pathway leading to the production of pro-inflammatory cytokines. However, CoCl2-treated monocytes do not fully differentiate into macrophage or DC, 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, pro-inflammatory state that can contribute to some of the pathologies associated with the exposure to this metal.

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