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: BeSO(4) induces cell death in monocytes but not in T lymphocytes, which instead respond by producing Interferon gamma (IFN-γ); conversely, CoCl(2) 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 CoCl(2)-treated monocytes is counteracted by the antiapoptotic activity of cytoplasmic p21(Cip1/WAF1), the activation of nuclear factor κB, and the inflammasome danger signaling pathway leading to the production of proinflammatory cytokines. However, CoCl(2)-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.
Department of Biology and Biotechnologies, Sapienza University of Rome, 70 00185 Rome, Italy. fabiana.paladini@uniroma1.it.
Fabiana
F
Paladini
Elisa
E
Cocco
Ilaria
I
Potolicchio
Henrieta
H
Fazekasova
Giovanna
G
Lombardi
Maria Teresa
MT
Fiorillo
Rosa
R
Sorrentino
D001608:Beryllium / Q000633:toxicity*; D003035:Cobalt / Q000633:toxicity*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D053583:Interleukin-1beta; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; C020711:beryllium sulfate; D003035:Cobalt; D007371:Interferon-gamma; C018021:cobaltous chloride; D001608:Beryllium