Low-level arsenic causes chronic inflammation and suppresses expression of phagocytic receptors.

Abstract

The impact of chronic low-level groundwater arsenic (As) exposure [in the range above the WHO-recommended limit of 10 μg/L but ≤50μg/L (permissible limit of As for many Asian countries)] was investigated for cross talk of inflammatory changes and expression of phagocytic receptors of exposed rural women (N, 45) from districts of 24 Parganas (south) and in matched control groups (N, 43) [As ≤10μg/L] from the same district. Systemic inflammation was evident from the upregulated levels of pro-inflammatory mediators like tumor necrosis factor-α (TNF-α); interleukins (ILs) like IL-6, IL-8, and IL-12; and C-reactive protein (CRP) in the sera and upregulated expression of protein kinase B phosphorylated at ser473 (pAKTser473)/nuclear factor-κB (NF-κB)/TNF-α axis in the leukocytes of exposed women with respect to control. We found that low-dose As exposure apart from inflicting inflammation altered the expression of phagocytic receptors-Fcγ receptors (FcγRs) and complement receptors (CRs). The leukocytes of the low-As-exposed women exhibited suppression of CD64, CD35, and CD11b and increased expression of CD16 with respect to control. Groundwater As showed a negative correlation with CD64 expression on monocytes [Pearson's r, -0.8205; 95% confidence interval (CI), -0.8789 to -0.7379] and granulocytes [r, -0.7635; 95% CI, -0.8388 to -0.6595] and a positive correlation with CD16 on granulocytes [r, 0.8363; 95% CI, 0.7599 to 0.8899]. A negative correlation of groundwater As was also observed with expression of CD35 on granulocytes [r, -0.8780; 95% CI, -0.9185 to -0.8192] and monocytes [r, -0.7778; 95% CI, -0.8490 to -0.6790] and CD11b on monocytes [r, -0.6035; 95% CI, -0.7218 to -0.4511]. Therefore, it may be indicated that chronic low-level As exposure (11-50μg/L) not only evoked chronic inflammatory changes but also suppressed the expression of FcγRs and CRs in the exposed women. This, in turn, may lead to susceptibility towards pathogenic infections or in long run may even contribute towards chronic inflammatory diseases including cancer.