Date of Award

1-1-1983

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Microbiology & Immunology

Abstract

Severe iron depletion has been associated with an increased susceptibility to infectious diseases. The purpose of this study was to assess phagocyte function and resistance to infection with Staphylococcus aureus during not only severe, but also moderate and marginal states of iron depletion.An experimental animal model of iron deficiency was developed in BALB/c mice. The amount of dietary iron supplementation was varied to attain different levels of iron deficiency. Tissue iron stores (liver, spleen, granulocyte), hemoglobins, and hematocrits correlated directly to the level of dietary iron supplementation. Comparison of food consumption and body weights of iron-deficient and sufficient animals indicated that protein-calorie malnutrition was not associated with iron depletion.Animals maintained on various levels of dietary iron were challenged with S. aureus via the tail vein. Iron-deficient animals exhibited consistently higher spleen bacterial titers. Staphylococci were recovered from the spleen of iron-depleted animals six to nine days after bacteria were cleared from the spleen of normal animals.White blood cell differentials were used to determine the relative number of peripheral blood granulocytes in iron-deficient vs. sufficient animals. The severe and moderately deficient animals had slightly fewer neutrophils than control animals.Granulocyte oxidative metabolism, assayed by nitroblue tetrazolium (NBT) reduction, was decreased significantly during severe, moderate, and mild iron depletion. When animals were reconstituted to normal iron levels, granulocyte NBT reduction returned to normal.Chemotaxis of polymorphonuclear (PMN) leukocytes was measured by a micropore filter method. Chemotactic migration of PMNs was impaired significantly at all levels of iron deficiency.The microbicidal capacity of granulocytes from iron-deficient animals was determined by an in vitro bactericidal assay. Ingestion and killing of S. aureus was impaired in phagocytes from severe, moderate, and marginally iron-depleted animals. Spectrophotometric measurement of the iron-dependent, microbicidal enzyme, myeloperoxidase, showed normal enzyme activity in PMNs from iron-deficient mice.The phagocytic response was impaired during severe, moderate, and mild iron deficiency in BALB/c mice as evidenced by inefficient clearance of S. aureus from the spleen and defects in phagocyte oxidative metabolism, bactericidal activity, and chemotaxis.

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