© 2002 American Thoracic Society DOI: 10.1165/rcmb.2001-0014OC Altered Zinc Homeostasis and Caspase-3 Activity in Murine Allergic Airway InflammationDepartment of Medicine, University of Adelaide, The Queen Elizabeth Hospital, Woodville, South Australia; Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra, A.C.T.; and Department of Clinical Biochemistry, Institute of Medical and Veterinary Science, South Australia, Australia. Address correspondence to: Dr P. Zalewski, Department of Medicine, University of Adelaide, The Queen Elizabeth Hospital, Woodville, South Australia, 5011 Australia. E-mail: peter.zalewski{at}adelaide.edu.au Zn may have an important protective role in the respiratory epithelium and Zn deficiency may enhance airway inflammation and epithelial damage. The effects of mild nutritional Zn deficiency on airway hyperresponsiveness (AHR) and airway inflammation in mice sensitized and challenged with ovalbumin (OVA) to induce an allergic response were investigated. Balb/c mice were given Zn normal (ZN, 50 mg/kg Zn) or Zn limited diets (ZL, 14 mg/kg Zn) before and during induction of allergic airway inflammation, with appropriate controls (saline-treated, SAL). ZL mice had greater levels of AHR than ZN mice, regardless of presence or absence of allergic inflammation. These mice also had increased eosinophilia and mucus cell hyperplasia compared with ZN mice. Second, ZN and ZL OVA-treated mice had significant decreases in airway epithelial Zinquin fluorescence, indicating a lowered availability of Zn compared with their SAL-treated counterparts. In contrast, the pro-apoptotic protein caspase-3, which was co-localized with Zn in the apical epithelium, was significantly increased in both ZN and ZL OVA-treated mice. Immunologically active caspase-3 and apoptosis were increased in OVA-treated mice, especially the ZL group. These findings provide the first data for adverse effects of Zn deficiency on the respiratory epithelium and support a role for altered Zn homeostasis and caspase upregulation in asthma.
Abbreviations: airway hyperreactivity, AHR • bronchoalveolar lavage fluid, BALF • basement membrane, BM • bovine serum albumin, BSA • fluoroscein isothiocyanate, FITC • grey scale intensity units, GSU • Hanks' balanced saline solution, HBSS • high power field, HPF • lumen, LM • metallothionein, MT • Optimum Cooling Tissue Medium, OCT • ovalbumin, OVA • phosphate-buffered saline, PBS • saline, SAL • N,N,N',N'-tetrakis(2-pyridylmethyl)ethyl-enediamine, TPEN • Zn-limited, ZL • Zn normal, ZN • zinc, Zn This article has been cited by other articles:
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