ISSN:
1365-3083
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
Exposure to environmental heavy metals has been reported to affect the immune system. Here, we tested the hypothesis that Hg+2, acting through membrane proteins, disrupts metabolic dynamics and downstream cell functions in human neutrophils. We found that HgCl2 inhibited: (1) polarization and (2) immunoglobulin (Ig)G-mediated phagocytosis of sheep erythrocytes in a dose-dependent manner from 2.5 to 10 µm. Because these activities have been linked with pro-inflammatory signalling, we also studied the effects of HgCl2 on intracellular signalling by measuring protein tyrosine phosphorylation. HgCl2 at doses = 1 µm increased tyrosine phosphorylation. We also studied the effect of HgCl2 on neutrophil metabolism by measuring NAD(P)H autofluorescence as an indicator of intracellular NAD(P)H concentration. After HgCl2 treatment, we found that normal sinusoidal NAD(P)H oscillations became incoherent. We recently reported that the NAD(P)H oscillation frequency is affected by cell migration and activation, which can in turn be regulated by integrin-mediated signalling. Therefore, we examined the effects of HgCl2 on cell surface distribution of membrane proteins. After exposure to environmentally relevant concentrations of HgCl2 we found that CR3, but not other membrane proteins (e.g. uPAR, FcγRIIA and the formyl peptide receptor), became clustered on cell surfaces. We suggest that HgCl2 disrupts integrin signalling/functional pathways in neutrophils.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1046/j.1365-3083.2001.00834.x
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