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DIMINISHED INJURY IN HYPOTRANSFERENEMIC MICE AFTER EXPOSURE TO A METAL-RICH PARTICLE
Citation:
Ghio, A J., J D. Carter, J H. Richards, K M. Crissman, H. Bobb, AND F. Yang. DIMINISHED INJURY IN HYPOTRANSFERENEMIC MICE AFTER EXPOSURE TO A METAL-RICH PARTICLE. AMERICAN JOURNAL PHYSIOLOGICAL LUNG CELL MOLECULAR PHYSIOLOGY. American Journal of Physiology, 278(5):L1051-L1061, (2000).
Description:
Using the hypotransferrinemic (Hp) mouse model, we studied the effect of altered iron homeostasis on the lung?s defense against catalytically active metal. The homozygotic (hpx/hpx) Hp mice had greatly diminished concentrations of both serum and lavage transferrin relative to wild-type mice and heterozygotes. Fifty Fg of a particle containing abundant concentrations of metals (a residual oil fly ash) was instilled into wild-type mice and heterozygotic and homozygotic Hp animals. There was an oxidative stress associated with particle exposure manifested by decreased lavage concentrations of ascorbate. However, rather than an increase in lung injury, diminished transferrin concentrations in homozygotic Hp mice were associated with decreased indices of damage including concentrations of relevant cytokines, inflammatory cell influx, lavage [protein], and lavage [LDH]. Comparable to other organs in the homozygotic Hp mouse, siderosis of the lung was evident with elevated concentrations of lavage and tissue iron. Consequent to these increased concentrations of iron, proteins to store and transport iron, ferritin and lactoferrin respectively, were increased when assayed by immunoprecipitation and immunohistochemistry. We conclude that altered iron homeostasis in the homozygotic Hp mouse lung resulted in the activation of ferritin and lactoferrrin genes. These two proteins can augment the antioxidant defense in the lower respiratory tract to diminish injury associated with an exposure to a metal-rich particle.