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

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 (0.0167–166.7 μg/cm²) were applied apically to NHBEs. After 18 h transepithelial potential difference (V_t), resistance (R_t), and short circuit current (I_sc) 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 (0.0167–16.7 μg/cm²) increased basal V_t. Only 16.7 μg/cm² GMA-MS increased basal V_t significantly. MMA-SS or GMA-MS exposure potentiated I_sc responses (decreases) to amiloride and bumetanide, while not affecting those to NPPB, GMA-MS to a lesser degree than MMA-SS. Variable effects on R_t 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 V_t, R_t, and I_sc 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. - Highlights: • Welding fume particle toxicity was investigated in human bronchial epithelial cells. • MMA-SS fume particles and GMA-MS particles were compared. • Both fumes activated epithelial Na⁺ channels, MMA-SS more potent than GMA-SS. • MMA-SS is more cytotoxic than GMA-SS with regard to LDH release. • Observed changes may help explain susceptibility to infection in workers.