Bacterial invasion of vertebrates triggers a marked reduction in the levels of iron associated with the plasma transferrin (Tf) pool. This hypoferremic response has been regarded as a host attempt to withhold essential iron from the invading pathogen. The exact nature of the mechanisms involved remains obscure. / The plasma Tf iron pool was studied with radiolabeled mouse Tf and its kinetics were determined in normal and infected mice. The plasma Tf iron pool of normal mice was dynamic with a half-life of 0.7 h. Iron left the plasma pool, entered the bone marrow, and was incorporated into erythrocytes. Studies with mice infected with Neisseria meningitidis revealed similar kinetics including no redistribution of iron within the various iron pools. Iron turnover in the Tf pool during the hypoferremic phase was also similar to control rates. Therefore, hypoferremia did not result from an accelerated removal of iron from the plasma Tf pool as previously suggested. These results implicate an impaired return of reticulo-endothelial (RE) system processed iron to the Tf pool during the hypoferremia. / The kinetics of iron processing by the RE system were studied by labeling the RE compartments with ('59)Fe-labeled denatured red blood cells. Uptake and redistribution of the label indicated the RE-processed iron was not returned to the plasma Tf pool during the hypoferremia. Fractionation of hepatic cellular compartments showed that this impaired release of iron resulted from a preferential incorporation of heme-derived iron into the intracellular ferritin pool and this produces the hypoferremia. / The role of ceruloplasmin (ferroxidase I,EC.1.16.3.1) (Cp) in iron metabolism during meningococcal infection was investigated. Plasma Cp ferroxidase activity was found to increase greatly in mice during the convalescence phase. Ferroxidase-deficient mice became hypoferremic as a result of an impaired return of heme-derived iron to plasma Tf. This hypoferremia was associated with an increased resistance to Neisseria meningitidis infection, an effect readily reversed by Cp supplementation or iron addition. This implicates Cp as an important component in the regulation of the plasma Tf iron pool. It also suggests that the increased levels of Cp during the acute phase response may serve to restore normal plasma Tf iron levels.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.71860 |
| Date | January 1984 |
| Creators | Letendre, Elaine. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Microbiology and Immunology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000218390, proquestno: AAINK66579, Theses scanned by UMI/ProQuest. |
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