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Trace element balance is changed in infected organs during acute Chlamydophila pneumoniae infection in mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Enheten för metallbiologisk forskning.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
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2008 (English)In: Biometals, ISSN 0966-0844, E-ISSN 1572-8773, Vol. 21, no 2, 229-237 p.Article in journal (Refereed) Published
Abstract [en]

Most infectious diseases are accompanied by changed levels of several trace elements in the blood. However, sequential changes in trace elements in tissues harbouring bacterial infections have not been studied. In the present study the respiratory pathogen Chlamydophila pneumoniae (C. pneumoniae), adapted to C57BL/6J mice, was used to study whether the balance of trace elements is changed in infected organs. Bacteria were quantitatively measured by real-time PCR in the blood, lungs, liver, aorta, and heart on days 2, 5, and 8 of the infection. Concentrations of 13 trace elements were measured in the liver, heart, and serum by inductively coupled plasma mass-spectrometry (ICP-MS). Infected mice developed expected clinical signs of disease and bacteria were found in lungs, liver, and heart on all days. The number of bacteria peaked on day 2 in the heart and on day 5 in the liver. The copper/zinc (Cu/Zn) ratio in serum increased as a response to the infection. Cu increased in the liver but did not change in the heart. Iron (Fe) in serum decreased progressively, whereas in the heart it tended to increase, and in the liver it progressively increased. C. pneumoniae may thus cause a changed trace element balance in target tissues of infection that may be pivotal for bacterial growth.

Place, publisher, year, edition, pages
2008. Vol. 21, no 2, 229-237 p.
Keyword [en]
Bacterial infection, Heart, Liver, Serum, Trace elements
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97118DOI: 10.1007/s10534-007-9114-7ISI: 000254087000015PubMedID: 17712530OAI: oai:DiVA.org:uu-97118DiVA: diva2:171916
Available from: 2008-04-25 Created: 2008-04-25 Last updated: 2010-05-31Bibliographically approved
In thesis
1. Chlamydophila pneumoniae in Cardiovascular Diseases: Clinical and Experimental Studies
Open this publication in new window or tab >>Chlamydophila pneumoniae in Cardiovascular Diseases: Clinical and Experimental Studies
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Chlamydophila pneumoniae (C. pneumoniae) has been suggested as a stimulator of chronic inflammation in atherosclerosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 50% of patients with stable angina pectoris or acute coronary syndrome undergoing coronary artery bypass grafting. C. pneumoniae mRNA, a marker of replicating bacteria, was demonstrated in 18% of the aortic biopsies.

Inflammation may have a role in the pathogenesis of thoracic aortic aneurysm, aortic dissection and aortic valve stenosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 26% of thoracic aortic aneurysm patients and in 11% of aortic dissection patients undergoing thoracic surgery and in 22% of stenotic aortic heart valves from patients undergoing aortic valve replacement. No bacterial mRNA was demonstrated in these aortic biopsies, nor in the valves, suggesting that the infection has passed into a persistent state. C. pneumoniae DNA was demonstrated in peripheral blood mononuclear cells in only 5% of aortic valve stenosis patients and not in thoracic aortic aneurysm or aortic dissection patients, suggesting that the bacterium disseminated to the cardiovascular tissue long before the patient required surgery. The copper/zinc ratio in serum, a marker of infection/inflammation, was significantly elevated in thoracic aortic aneurysm patients, supporting an inflammatory pathogenesis. Patients positive for C. pneumoniae in the aortic valve had more advanced coronary atherosclerosis, further supporting a possible role for C. pneumoniae in atherosclerosis.

Mice were infected with C. pneumoniae that disseminated to all organs investigated (i.e. lungs, heart, aorta, liver and spleen). Trace element concentrations were altered in infected animals with an increased copper/zinc ratio in serum, a progressively increased iron concentration in the liver and a progressively decreased iron concentration in serum. Iron is important for C. pneumoniae metabolism, and a changed iron homeostasis was noted in infected mice by alterations in iron-regulating proteins, such as DMT1 and hepcidin.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 71 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 340
Keyword
Communicable diseases, Chlamydophila pneumoniae, Chlamydia pneumoniae, trace elements, atherosclerosis, aortic valve stenosis, thoracic aortic aneurysm, aortic dissection, hepcidin, iron, Infektionssjukdomar
Identifiers
urn:nbn:se:uu:diva-8667 (URN)978-91-554-7176-7 (ISBN)
Public defence
2008-05-23, Hörsalen, Akademiska sjukhuset, ing. D1, Dag Hammarsköldsväg 17, Uppsala, 09:15
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Available from: 2008-04-25 Created: 2008-04-25Bibliographically approved

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