Alcohol-Mediated Zinc Deficiency Within the Alveolar Space: A Potential Fundamental Mechanism Underlying Oxidative Stress and Cellular Dysfunction in the Alcoholic Lung

Abstract

Zinc is one of the most abundant trace elements in the human body, and its presence is essential for numerous biological processes including enzymatic activity, immune function, protein synthesis, and wound healing. Given these important roles, zinc has a sophisticated transport system to regulate its homeostasis. Determination of zinc status, however, is difficult to determine as serum levels are closely maintained and are not an accurate reflection of total body zinc or metabolism at the organ level. Fortunately, the discovery of zinc-specific fluorescent dyes has allowed for a much better assessment of zinc status in the respiratory system and has revealed that alcoholism perturbs this highly developed zinc metabolism such that its distribution to the lung and alveolar space is significantly decreased. As a result, this pulmonary zinc deficiency impairs function in the alveolar macrophage, which is the primary host immune cell within the lower airway. Experimental models have demonstrated that correction of this zinc deficiency restores immune function to the alveolar macrophage as best reflected by improved bacterial clearance in response to infection. While the precise mechanisms underlying alcohol-induced zinc deficiency are still under investigation, there is experimental evidence of several important connections with granulocyte–macrophage colony-stimulating factor and oxidative stress, suggesting that alteration of zinc homeostasis may be a fundamental mechanism underlying the cellular pathology seen in the alcohol lung phenotype. This chapter reviews zinc homeostasis and offers insight into our understanding of zinc deficiency in the setting of alcoholism and the potential of zinc as a therapeutic modality in the vulnerable alcoholic host. (PsycINFO Database Record (c) 2016 APA, all rights reserved)