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

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. [ABSTRACT FROM PUBLISHER]