Ceruloplasmin and regulation of transferrin iron during Neisseria meningitidis infection in mice

The role of ceruloplasmin (ferroxidase I; EC 1.16.3.1) in iron metabolism during experimental Neisseria meningitidis infection was investigated. Plasma ceruloplasmin activity was found to increase greatly in mice during the covalescence phase of iron-controlled infection and after a plasma hypoferremia had occurred. Ceruloplasmin activity-deficient animals became hypoferremic as a result of an impaired release of iron from the reticuloendothelial system as shown by impaired return of reticuloendothelial system-processed heme iron in these mice. Hypoferremia in ceruloplasmin activity-deficient mice was associated with an increased resistance to N. meningitidis infection, an effect reversed readily by ceruloplasmin supplementation or iron addition. This evidence implicated ceruloplasmin activity as an important component in the regulation of the plasma transferrin iron pool and suggested that an important role of additional ceruloplasmin as an acute-phase protein might be related to the requirement of additional transferrin iron. This study also provided further evidence of the importance of transferrin iron and host hypoferremia in bacterial infection.