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

TY - JOUR

T1 - Divergent Effect of Cobalt and Beryllium Salts on the Fate of Peripheral Blood Monocytes and T Lymphocytes

AU - Paladini, Fabiana

AU - Cocco, Elisa

AU - Potolicchio, Ilaria

AU - Fazekasova, Henrieta

AU - Lombardi, Giovanna

AU - Fiorillo, Maria Teresa

AU - Sorrentino, Rosa

PY - 2011

Y1 - 2011

N2 - 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-gamma); 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 p21(Cip1/WAF1), the activation of nuclear factor kappa B, 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.

AB - 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-gamma); 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 p21(Cip1/WAF1), the activation of nuclear factor kappa B, 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.

U2 - 10.1093/toxsci/kfq328

DO - 10.1093/toxsci/kfq328

M3 - Article

SN - 1096-0929

VL - 119

SP - 257

EP - 269

JO - Toxicological Sciences

JF - Toxicological Sciences

IS - 2

ER -