Antonio Arciniegas, MD
Rank
Fellow or Postdoc
Department
Medicine
Pulmonary and Critical Care Medicine
Authors
Antonio Arciniegas Rubio, MD*, Jack Varon, MD, Josh Englert, MD, Rebecca Baron, MD
Principal Investigator
Rebecca Baron, MD
Twitter / Website
Categories
Rationale: Zinc deficiency exacerbates acute lung injury induced by cell stretch in preclinical models. Critically ill patients with low plasma zinc levels have an increased risk of acute respiratory distress syndrome (ARDS). The protective role of zinc supplementation ARDS is unclear, since low plasma zinc levels may result from dietary deficiency or redistribution into tissues during illness. We hypothesized that specific zinc importers mediate plasma zinc transition into lung epithelial cells and protect against cell-stretch mediated lung injury.
Methods and Results: A549 human lung epithelial cells were exposed to cyclic stretch with or without zinc deficiency induced by the chelator TPEN. Two zinc importers were significantly induced during stretch and zinc deficiency, and their knockdown inhibited cytoprotective metallothionein (MT) expression. In mice, these importers were upregulated during LPS- and ventilator-induced lung injury, and zinc supplementation reduced lung dysfunction vs. saline (elastance 61.9% vs. 95.6%, p<0.05). Zinc-treated mice showed increased zinc concentrations in liver, plasma, and lung. In ventilated sepsis patients from a clinical trial, zinc supplementation increased ZIP transporter expression in PMBCs (ZIP14, zinc vs. placebo, P<0.05). Conclusions: Plasma zinc and zinc importer levels point toward mechanisms of zinc in mediating protection against cell-stretch lung injury, warranting further studies.