Turnover in the transferrin iron pool during the hypoferremic phase of experimental Neisseria meningitidis infection in mice

Abstract

Mouse transferrin was used to specifically label the plasma transferrin Fe pool for studies of Fe kinetics in normal mice and infected mice during the hypoferremic phase of experimental meningococcal infection. The plasma transferrin Fe pool of normal mice was very dynamic, with a half-life of Fe in the pool of 0.7 h. Fe left the plasma pool, entered the bone marrow and was released into the blood in erythrocytes. Fe from the transferrin pool also entered the liver and spleen, and was presumably in the RES components of these organs. Most of the Fe that had been supplied as transferrin Fe was found in erythrocytes by 48 h after injection. Studies with mice infected with N. meningitidis strain M1011 revealed similar kinetics for transferrin Fe. There was no redistribution of Fe within the various Fe pools as a result of infection. Fe turnover in the plasma transferrin pool during the hypoferremic phase was similar to control rates; Fe leaving the pool entered its normal erythroid compartments. The lack of accelerated turnover of plasma Fe and the finding that plasma Fe was not rerouted to storage compartments during the hypoferremic phase provided good evidence that lactoferrin and leukocytic endogenous mediator were not directly involved in redirecting transferrin Fe. This evidence implicates an impaired return of RES-processed Fe to the transferrin pool during the hypoferremic response. This appears to be a logical point in the erythroid Fe cycle for host-mediated Fe sequestration, since the RES is involved in Fe storage and may regulate Fe levels in the plasma transferrin pool under normal conditions.