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.
Paladini
Fabiana
F
Department of Biology and Biotechnologies, Sapienza University of Rome, 70 00185 Rome, Italy. fabiana.paladini@uniroma1.it.
Cocco
Elisa
E
Potolicchio
Ilaria
I
Fazekasova
Henrieta
H
Lombardi
Giovanna
G
Fiorillo
Maria Teresa
MT
Sorrentino
Rosa
R
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