Altered Ion Transport in Normal Human Bronchial Epithelial (NHBE) Cells Following Exposure to Metal Welding Particles

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Inhalation of welding fumes is associated with adverse effects in the pulmonary system, including susceptibility to infection. Several types of welding processes occur, giving rise to fumes of different compositions. In this study we investigated the effects of particles derived from fumes generated from manual metal arc‐stainless steel (MMA‐SS) and gas metalarc‐mild steel (GMA‐MS) welding on ion transport in NHBE in culture. The toxicities and the composition of the particles generated during MMA‐SS and GMA‐MS processes are different. MMA‐SS particles are more soluble and contain Cr, Ni, Fe and Mn, whereas GMA‐MS particles are less soluble and contain Fe and Mn. Ion transport is critical to the maintenance of the airway surface liquid. We hypothesized that epithelial cells are targets of inhaled welding fumetoxicity. NHBE (Lonza) were cultured in submersion culture for 3 days followed by 21 d in air‐interface on permeable inserts; cells with transepithelial resistance (Rt) >1000 Ω·cm2were used. Generated MMA‐SS or GMA‐MS particles collected on filters were suspended in medium and applied (50 μl) to the apical chamber. The doses of both types of particles ranged from 0.0167 to166.7 μg/cm2. After 18 h of incubation the inserts were placed in Ussing chambers for the measurement of transepithelial potential difference (Vt), short circuit current (Isc) and Rt. The effects of fume exposure on Na+ and Cl− channels, the Na+,K+,2Cl−‐cotransporter and the Na+,K+‐pump, were evaluated by applying the following inhibitors, respectively: amiloride(A; apical; 3×10−5 M), NPPB (N; apical; 10−4 M), bumetanide (B; 10−4 M) and ouabain (O; basolateral; 10−4M). Changes in lactate dehydrogenase(LDH) levels in apical medium also were assessed after exposure. Following exposure, 0.0167–16.7 μg/cm2MMA increased basal Vt. Only16.7 μg/cm2 GMA‐MS increased basal Vt. MMA‐SS exposure potentiated Isc responses (decreases in Isc) to A and B, while not affecting those to N and O. Likewise, exposure to GMA‐MS potentiated Isc responses to A and B, but to a lesser degree than observed after MMA‐SS exposure. Variable effects on Rt were observed in response to A, B and O. Generally, MMA‐SS was more potent in altering responses to A and B than GMA‐MS. MMA‐SS evoked greater increases in LDH release than GMA‐MS, but bioelectric changes occurred in the absence of increased LDH release. Our findings indicate that both apical Na+ transport and basolateral Na+,K+,2Cl−‐cotransportin airway epithelium is affected by fume particle exposure. The greater effect of MMA‐MS compared to GMA‐MS might reflect the actions of soluble metals. Enhanced Na+ absorption and decreased airway surface liquid could compromise lung defenses against infection.Support or Funding InformationSupported by NIOSH