Zinc There have been numerous reviews focusing on the impor- tance of vitamin C, vitamin E and selenium for respiratory diseases such as asthma, but limited studies are available on the role of dietary zinc (Zn). This paper will attempt to review the current state of knowledge, while also proposing the possible importance of Zn in the context of the respira- tory system. Zinc is a group IIb dietary metal required for the healthy functioning of the body. The Australian recommended dietary intake of Zn is approximately 12 mg/day and this is obtain- able from protein-rich foods, such as red meats, seafood, fresh fruit and vegetables, and dairy products. Over the past 30 years, many researchers have demonstrated the critical role of Zn in a variety of physiological processes, including growth and development, maintenance and priming of the immune system and tissue repair and regeneration. 1 As Zn is the most widely used biometal in biology, it can be found in all organs, secretions, fluids and tissues of the body and is transported via albumin in the circulation. 1 Zinc possesses two main properties, which make it an ideal par- ticipator in biological systems. First, Zn is virtually non-toxic as the homeostatic mechanism by which it is regulated is so efficient that no chronic disorders are known to be associated with excessive accumulation. 2 Second, its physical and chem- ical properties enable it to interact with a variety of enzymes and other proteins that participate in cellular metabolism as well as in the control of gene transcription. 3 In the body Zn exists in two main states: (i) a bound form that is held on to tightly by metalloproteins and Zn finger proteins; and (ii) a more loosely bound labile form that participates in intracellular Zn fluxes and is readily depleted in Zn deficiency. Although all organs contain labile intra- cellular Zn, the following tissues are particularly labile Zn rich: hippocampus, testis and secretory cells (e.g. pancreatic β cells and mast cells). 4 Respiratory epithelium The respiratory epithelium is a complex and highly-regulated inert barrier separating the human airway from the external environment and is therefore constantly exposed to a variety of exogenous agents (e.g. allergens, inhaled pollutants and viruses) capable of initiating an inflammatory reaction. Although this epithelium is fundamentally a protective barrier, one of its important roles is to produce cytokines, growth factors, nitric oxide, matrix metalloproteinases and many pro- and anti-inflammatory substances. 5 Hence the potential for enhanced oxidative stress, due to the involve- ment of the epithelium in airway inflammation and continual exposure to exogenous environmental agents, is greatly enhanced in this tissue. 6 Airway epithelial damage has been well reported in aller- gic diseases, such as asthma, where tissue injury leads to epithelial desquamation and shedding. This is due to the recruitment and activation of inflammatory cells, such as the eosinophils, mast cells and neutrophils, which release tissue- damaging proteases, chemotactic cytokines and toxic reactive oxygen species thereby exacerbating the allergic response. 5 Why zinc may be beneficial for the respiratory tract Zinc has been shown to be vital as an anti-oxidant, micro- tubule stabilizer, anti-apoptotic agent, growth cofactor and Immunology and Cell Biology (2001) 79, 170–177 Special Feature New insights into the role of zinc in the respiratory epithelium AI Q TRUONG-TRAN, JOANNE CARTER, RICHARD RUFFIN and PETER D ZALEWSKI Department of Medicine, University of Adelaide, The Queen Elizabeth Hospital, Woodville, South Australia, Australia Summary Over the past 30 years, many researchers have demonstrated the critical role of zinc (Zn), a group IIb metal, in diverse physiological processes, such as growth and development, maintenance and priming of the immune system, and tissue repair. This review will discuss aspects of Zn physiology and its possible beneficial role in the respiratory epithelium. Here we have detailed the mechanisms by which Zn diversely acts as: (i) an anti- oxidant; (ii) an organelle stabilizer; (iii) an anti-apopototic agent; (iv) an important cofactor for DNA synthesis; (v) a vital component for wound healing; and (vi) an anti-inflammatory agent. This paper will also review studies from the authors’ laboratory concerning the first attempts to map Zn in the respiratory epithelium and to elucidate its role in regulating caspase-3 activated apoptosis. We propose that Zn, being a major dietary anti-oxidant has a protective role for the airway epithelium against oxyradicals and other noxious agents. Zn may therefore have important implications for asthma and other inflammatory diseases where the physical barrier is vulnerable and compromised. Key words: anti-oxidant, epithelium, inflammation, respiratory, zinc. Correspondence: AQ Truong-Tran, Department of Medicine, University of Adelaide, The Queen Elizabeth Hospital, Woodville, South Australia 5011, Australia. Email: ai.truong-tran@student.adelaide.edu.au Received 10 October 2000; accepted 10 October 2000.