Diminished injury in hypotransferrinemic mice after exposure to a metal-rich particle

Using the hypotransferrinemic (Hp) mouse model, we studied the effect of al tered iron homeostasis on the defense of the lung against a catalytically a ctive metal. The homozygotic (hpx/hpx) Hp mice had greatly diminished conce ntrations of both serum and lavage fluid transferrin relative to wild-type mice and heterozygotes. Fifty micrograms of a particle containing abundant concentrations of metals (a residual oil fly ash) was instilled into wild-t ype mice and heterozygotic and homozygotic Hp animals. There was an oxidati ve stress associated with particle exposure as manifested by decreased lava ge fluid concentrations of ascorbate. However, rather than an increase in l ung injury, diminished transferrin concentrations in homozygotic Hp mice we re associated with decreased indexes of damage, including concentrations of relevant cytokines, inflammatory cell influx, lavage fluid protein, and la vage fluid lactate dehydrogenase. Comparable to other organs in the homozyg otic Hp mouse, siderosis of the lung was evident, with elevated concentrati ons of lavage fluid and tissue iron. Consequent to these increased concentr ations of iron, proteins to store and transport iron, ferritin, and lactofe rrin, respectively, were increased when assayed by immunoprecipitation and immunohistochemistry. We conclude that the lack of transferrin in Hp mice d id not predispose the animals to lung injury after exposure to a particle a bundant in metals. Rather, these mice demonstrated a diminished injury that was associated with an increase in the metal storage and transport protein s.