Inorganic arsenic can be potent granulotoxin in mammalian neutrophils in vitro

Abstract

An important outcome arising out of occupational/environmental exposure to arsenic (As) is immunotoxicity. To determine the impact of inorganic As on innate immune cells, effects of a low dose of NaAsO₂ (i.e. 20 ng As/ml) on select parameters associated with human and bovine neutrophils (PMN) were evaluated in vitro. PMN isolated from the blood of healthy individuals and cows (n = 8/treatment) were pre-incubated with NaAsO₂ for 12 h before effects on PMN phagocytosis, transcription of TLR2, TLR4 and CD64 in human PMN – as well as on phagocytosis-dependent/-independent cell chemiluminescence (CL), phagocytosis and killing of Staphylococcus aureus and Escherichia coli, PMN H₂O₂ production and necrosis and TLR4 transcription in bovine PMN – were assessed. Relative to control (no As) PMN, treatment with As significantly decreased phagocytic capacity and CD64 mRNA, but increased TLR2 and TLR4 mRNA, in human PMN. In bovine PMN, while As also led to increased TLR4 mRNA abundance, it resulted in decreases in phagocytosis-dependent and -independent CL, PMN H₂O₂ production, PMN phagocytosis and killing of both E. coli and S. aureus by PMN. Considering the broad roles of PMN in immunology, the results of these studies increase our understanding of functional consequences of As exposure in inducing immunotoxicity and increasing susceptibility to (infectious) diseases in mammals.

Keywords:

• Chemiluminescence
• flow cytometry
• inorganic arsenic
• necrosis
• neutrophils TLR

Disclosure statement

The authors declare no conflicts of interest. The authors alone are responsible for the content of this manuscript.

Funding

This study was supported by the Ferdowsi University of Mashhad and Payamnoor University of Mashhad.