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Title: Iron metabolism in macrophages
Author: Alvarez-Hernandez, Javier
ISNI:       0000 0001 3418 7422
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1985
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A study has been made of intracellular events in the iron metabolism of resident, immunologically- and nonimmunologically-provoked mouse peritoneal macrophages, to clarify the relationship between iron release and intracellular iron metabolism of the mononuclear phagocyte system in normal and inflammatory conditions. The dynamics and magnitude of peritoneal infiltration of those cells populations that are generated by intraperitoneal inoculation of Corynebacterium Earvum or thioglycollate broth were characterized and compared with the resident population present in unstimulated mice. The cellular influx differed according to the stimulus inoculated, the major differences being that the neutrophil influx was in a two-wave mode in C. parvum-inoculated mice in contrast to only a one-wave mode in thioglycolate broth-inoculated mice. Macrophage morphological changes and the absolute numbers of macrophages were also observed. After 4 days post-stimulation the total yield per mouse of thioglycollate broth-elicited macrophages (tM) was more than 3 times that from C. parvum-inoculated mice (CpM) and CpM yields were 2.5 times that of resident macrophages (rM). Macrophages from inoculated mice differed morphologically from rM. The stimulated cells were found to be a young population, tM being more immature than CpM. The identification of lave cells was used to contrast the macrophage populations and it was found that while the rM and CpM contained similar percentages of lave cells tM had a lower percentage. But when expressed in absolute numbers tM and CpM appeared to contain a similar number of lave cells, which was double that of rM. These three population of macrophages were pulsed with [59]Fe-[125]I-tranferrin-antitransferrin immune complexes ([59]Fe-[125]I-antiTf) and release of [59]Fe and [125]I measured. It was found that tM and CpM processed the immune complexes more rapidly than rM, but that there was an impairment of Fe release by tM compared with rM and CpM, which, when release was related to release of [125]I (degradation of complexes), were similar to each other. A sensitive IRMA assay was developed for measuring mouse ferritin (Ft) with which Ft release and intracellular Ft levels were determined. None of the experiments designed to test Ft secretion by macrophages supported an active release process, and it was concluded that if peritoneal macrophages release Ft is mainly due to cell leakeage and not by secretion. It was found that tM had a lower Ft and Fe content than CpM and rM, but the ratio (Ft:Fe) was higher in tM than in CpM or rM, in both of which it was similar. These results implied the posibility that tM contain Ft molecules more loaded with Fe than rM and CpM. Synthesis of Ft was measured by 3H-leucine incorporation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biochemistry