liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
TNF-alpha preserves lysosomal stability in macrophages: A potential defense against oxidative lung injury
Linköping University, Department of Medicine and Health Sciences, Pulmonary Medicine . Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Respiratory Medicine.
Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences.
2010 (English)In: TOXICOLOGY LETTERS, ISSN 0378-4274, Vol. 192, no 2, 261-267 p.Article in journal (Refereed) Published
Abstract [en]

Iron-catalyzed oxidative damage on the respiratory epithelium is prevented by alveolar macrophages depositing iron inside their lysosomes. Bound in an un-reactive state to various metalloproteins, e.g. ferritin, most lysosomal iron is kept separated from reactive oxygen species (ROS) by intracellular anti-oxidative enzyme systems. Some ROS may, however, escape this protective shield of antioxidants, react with small amounts of free redox-active iron within lysosomes, thereby causing peroxidative damage on lysosomes and possibly also ensuing cell death. Since macrophages, containing large amounts of lysosomal iron, are very resistant to TNF-alpha, we hypothesized that this cell type has developed specific defense mechanisms against TNF-alpha-induced ROS generation. Murine macrophages were exposed (or not) to non-toxic concentrations of TNF-alpha and/or iron and were then challenged with H2O2. Iron-exposed oxidatively stressed cells exhibited extensive lysosomal disruption resulting in pronounced cell death. In contrast, TNF-alpha stabilized lysosomes and protected cells, particularly those iron-exposed, by reducing cellular iron and increasing H-ferritin. Intracellular generation of H2O2 under oxidative stress was kept unchanged by TNF-alpha and/or iron. However, TNF-alpha increased basal levels of glutathione by up-regulating the synthesis of gamma-glutamylcystein synthetase, thereby strengthening the anti-oxidative capacity. TNF-alpha inhibitors would block this novel anti-oxidative defense system, possibly explaining their adverse effects on the lung.

Place, publisher, year, edition, pages
2010. Vol. 192, no 2, 261-267 p.
Keyword [en]
Apoptosis, Ferritin, Inflammation, Lysosomes, Oxidative stress
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-54247DOI: 10.1016/j.toxlet.2009.10.031ISI: 000274743300025OAI: diva2:302304
Available from: 2010-03-05 Created: 2010-03-05 Last updated: 2010-12-21

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Persson, LennartVainikka, Linda
By organisation
Pulmonary Medicine Experimental Pathology Faculty of Health SciencesDepartment of Respiratory Medicine
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 54 hits
ReferencesLink to record
Permanent link

Direct link