Mercury inhibition of neutrophil activity: evidence of aberrant cellular signalling and incoherent cellular metabolism.
Mercury inhibition of neutrophil activity: evidence of aberrant cellular signalling and incoherent cellular metabolism.
复制标题
汞对中性粒细胞活性的抑制：异常细胞信号传导和不连贯细胞代谢的证据。
DOI：
10.1046/j.1365-3083.2001.00834.x
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发表时间：
2001
影响因子：
3.7
通讯作者：
Petty,HR
中科院分区：
文献类型：
--
作者：
Worth,RG;Esper,RM;Warra,NS;Kindzelskii,AL;Rosenspire,AL;Todd3rd,RF;Petty,HR
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 HgCl2inhibited: (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 HgCl2on intracellular signalling by measuring protein tyrosine phosphorylation. HgCl2at doses = 1 µmincreased tyrosine phosphorylation. We also studied the effect of HgCl2on neutrophil metabolism by measuring NAD(P)H autofluorescence as an indicator of intracellular NAD(P)H concentration. After HgCl2treatment, 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 HgCl2on cell surface distribution of membrane proteins. After exposure to environmentally relevant concentrations of HgCl2we 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 HgCl2disrupts integrin signalling/functional pathways in neutrophils.
