Altered ion transport in normal human bronchial epithelial cells following exposure to chemically distinct metal welding fume particles

Toxicol Appl Pharmacol. 2017 Jul 1:326:1-6. doi: 10.1016/j.taap.2017.04.008. Epub 2017 Apr 12.

Abstract

Welding fume inhalation causes pulmonary toxicity, including susceptibility to infection. We hypothesized that airway epithelial ion transport is a target of fume toxicity, and investigated the effects of fume particulates from manual metal arc-stainless steel (MMA-SS) and gas metal arc-mild steel (GMA-MS) on ion transport in normal human bronchial epithelium (NHBE) cultured in air-interface. MMA-SS particles, more soluble than GMA-MS particles, contain Cr, Ni, Fe and Mn; GMA-MS particles contain Fe and Mn. MMA-SS or GMA-MS particles (0.0167-166.7μg/cm2) were applied apically to NHBEs. After 18h transepithelial potential difference (Vt), resistance (Rt), and short circuit current (Isc) were measured. Particle effects on Na+ and Cl¯ channels and the Na+,K+,2Cl¯-cotransporter were evaluated using amiloride (apical), 5-nitro-2-[(3-phenylpropyl)amino]benzoic acid (NPPB, apical), and bumetanide (basolateral), respectively. MMA-SS (0.0167-16.7μg/cm2) increased basal Vt. Only 16.7μg/cm2 GMA-MS increased basal Vt significantly. MMA-SS or GMA-MS exposure potentiated Isc responses (decreases) to amiloride and bumetanide, while not affecting those to NPPB, GMA-MS to a lesser degree than MMA-SS. Variable effects on Rt were observed in response to amiloride, and bumetanide. Generally, MMA-SS was more potent in altering responses to amiloride and bumetanide than GMA-MS. Hyperpolarization occurred in the absence of LDH release, but decreases in Vt, Rt, and Isc at higher fume particulate doses accompanied LDH release, to a greater extent for MMA-SS. Thus, Na+ transport and Na+,K+,2Cl¯-cotransport are affected by fume exposure; MMA-MS is more potent than GMA-MS. Enhanced Na+ absorption and decreased airway surface liquid could compromise defenses against infection.

Keywords: Air-interface; Airway epithelium; Cell culture; Ion channels; Ion transport; Lactate dehydrogenase; Welding fume.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Air Pollutants, Occupational / toxicity*
  • Bronchi / drug effects*
  • Bronchi / metabolism
  • Bronchi / pathology
  • Cells, Cultured
  • Chloride Channels / drug effects
  • Chloride Channels / metabolism
  • Dose-Response Relationship, Drug
  • Electric Impedance
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Epithelial Sodium Channel Agonists / toxicity*
  • Epithelial Sodium Channels / drug effects*
  • Epithelial Sodium Channels / metabolism
  • Gases
  • Humans
  • Inhalation Exposure / adverse effects
  • Ion Transport / drug effects
  • L-Lactate Dehydrogenase / metabolism
  • Membrane Potentials
  • Occupational Exposure / adverse effects
  • Sodium-Potassium-Chloride Symporters / drug effects*
  • Sodium-Potassium-Chloride Symporters / metabolism
  • Stainless Steel / toxicity
  • Steel / toxicity*
  • Time Factors
  • Welding*

Substances

  • Air Pollutants, Occupational
  • Chloride Channels
  • Epithelial Sodium Channel Agonists
  • Epithelial Sodium Channels
  • Gases
  • Sodium-Potassium-Chloride Symporters
  • Stainless Steel
  • Steel
  • L-Lactate Dehydrogenase