TNF-alpha-stimulated macrophages protect A549 lung cells against iron and oxidation
2013 (English)In: Experimental and Toxicological Pathology, ISSN 0940-2993, E-ISSN 1618-1433, Vol. 65, no 1-2, 81-89 p.Article in journal (Refereed) Published
Previously, we have shown that TNF-alpha protects iron-exposed J774 macrophages against iron-catalyzed oxidative lysosomal disruption and cell death by increasing reduced glutathione and H-ferritin in cells. Because J774 cells are able to harbor large amounts of iron, which is potentially harmful in a redox-active state, we hypothesized that TNF-alpha-stimulated J774 macrophages will prevent iron-driven oxidative killing of alveolar epithelial A549 cells in co-culture. In the present study, iron trichloride (which is endocytosed by cells as hydrated iron-phosphate complexes) was mainly deposited inside the lysosomes of J774 macrophages, while A549 cells, equally iron exposed, accumulated much less iron. When challenged by oxidants, however, reactive lysosomal iron in A549 cells promoted lysosomal disruption and cell death, particularly in the presence of TNF-alpha. This effect resulted from an elevation in ROS generation by TNF-alpha, while a compensatory upregulation of protective molecules (H-ferritin and/or reduced glutathione) by TNF-alpha was absent. A549 cell death was particularly pronounced when iron and TNF-alpha were present in the conditioned medium during oxidant challenge; thus, iron-driven oxidative reactions in the culture medium were a much greater hazard to A549 cells than those taking place inside their lysosomes. Consequently, the iron chelator, deferoxamine, efficiently prevented A549 cell death when added to the culture medium during an oxidant challenge. In co-cultures of TNF-alpha-stimulated lung cells, J774 macrophages sequestered iron inside their lysosomes and protected A549 cells from oxidative reactions and cell death. Thus, the collective effect of TNF-alpha on co-cultured lung cells was mainly cytoprotective.
Place, publisher, year, edition, pages
Elsevier , 2013. Vol. 65, no 1-2, 81-89 p.
Apoptosis, Ferritin, Fibrosis, Lysosomes, Macrophages, Oxidative stress
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-89525DOI: 10.1016/j.etp.2011.06.004ISI: 000314006000014OAI: oai:DiVA.org:liu-89525DiVA: diva2:608231
Funding Agencies|County Council of Ostergotland (ALF)||Medical Research Council of Southeast Sweden (FORSS)||Swedish Medical Society||Linkoping Medical Society||Olle Engkvist, Apotekare Hedberg and LiO (Ostergotland, Sweden)||2013-02-262013-02-262014-03-03