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Red blood cells upregulate cytoprotective proteins and the labile iron pool in dividing human T cells despite a reduction in oxidative stress

Fonseca, Ana Mafalda; Pereira, Carlos F. LU ; Porto, Graça and Arosa, Fernando A. (2003) In Free Radical Biology and Medicine 35(11). p.1404-1416
Abstract

We have recently reported that red blood cells (RBC) promote T cell growth and survival by inhibiting activation-induced T cell death. In the present study, we have examined parameters of oxidative stress and intracellular iron in activated T cells and correlated these data with the expression of ferritin, heme oxygenase-1 (HO-1), and the transferrin receptor CD71. T cells growing in the presence of RBC had reduced levels of reactive oxygen species (ROS) and oxidatively modified proteins, suggesting that RBC efficiently counteracted ROS production on the activated T cells. Flow cytometry and immunodetection demonstrated that T cells dividing in the presence of RBC had increased levels of intracellular ferritin rich in L-subunits and... (More)

We have recently reported that red blood cells (RBC) promote T cell growth and survival by inhibiting activation-induced T cell death. In the present study, we have examined parameters of oxidative stress and intracellular iron in activated T cells and correlated these data with the expression of ferritin, heme oxygenase-1 (HO-1), and the transferrin receptor CD71. T cells growing in the presence of RBC had reduced levels of reactive oxygen species (ROS) and oxidatively modified proteins, suggesting that RBC efficiently counteracted ROS production on the activated T cells. Flow cytometry and immunodetection demonstrated that T cells dividing in the presence of RBC had increased levels of intracellular ferritin rich in L-subunits and HO-1 along with a downmodulation in CD71 expression. Finally, using the fluorescent iron indicator calcein and flow cytometry analysis, we were able to show that a relative amount of the labile iron pool (LIP) was upregulated in T cells growing in the presence of RBC. These findings are consistent with a typical response to iron overload. However, neither heme compounds nor ferric iron reproduced the levels of expansion and survival of T cells induced by intact RBC. Altogether, these data suggest that RBC inhibit apoptosis of activated T cells by a combination of ROS scavenging and upregulation of cytoprotective proteins such as ferritin and HO-1, which may counteract a possible toxic effect of the increased intracellular free iron.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Apoptosis, Ferritin, Free radicals, Growth, Heme oxygenase, Iron, Oxidative stress, Red blood cells, Survival, T cells, Transferrin receptor
in
Free Radical Biology and Medicine
volume
35
issue
11
pages
13 pages
publisher
Elsevier
external identifiers
  • scopus:0344875071
ISSN
0891-5849
DOI
10.1016/j.freeradbiomed.2003.08.011
language
English
LU publication?
no
id
5d1e6ed8-d7b1-4e4e-925f-841719c1a8a7
date added to LUP
2017-10-02 17:35:36
date last changed
2018-01-07 12:20:22
@article{5d1e6ed8-d7b1-4e4e-925f-841719c1a8a7,
  abstract     = {<p>We have recently reported that red blood cells (RBC) promote T cell growth and survival by inhibiting activation-induced T cell death. In the present study, we have examined parameters of oxidative stress and intracellular iron in activated T cells and correlated these data with the expression of ferritin, heme oxygenase-1 (HO-1), and the transferrin receptor CD71. T cells growing in the presence of RBC had reduced levels of reactive oxygen species (ROS) and oxidatively modified proteins, suggesting that RBC efficiently counteracted ROS production on the activated T cells. Flow cytometry and immunodetection demonstrated that T cells dividing in the presence of RBC had increased levels of intracellular ferritin rich in L-subunits and HO-1 along with a downmodulation in CD71 expression. Finally, using the fluorescent iron indicator calcein and flow cytometry analysis, we were able to show that a relative amount of the labile iron pool (LIP) was upregulated in T cells growing in the presence of RBC. These findings are consistent with a typical response to iron overload. However, neither heme compounds nor ferric iron reproduced the levels of expansion and survival of T cells induced by intact RBC. Altogether, these data suggest that RBC inhibit apoptosis of activated T cells by a combination of ROS scavenging and upregulation of cytoprotective proteins such as ferritin and HO-1, which may counteract a possible toxic effect of the increased intracellular free iron.</p>},
  author       = {Fonseca, Ana Mafalda and Pereira, Carlos F. and Porto, Graça and Arosa, Fernando A.},
  issn         = {0891-5849},
  keyword      = {Apoptosis,Ferritin,Free radicals,Growth,Heme oxygenase,Iron,Oxidative stress,Red blood cells,Survival,T cells,Transferrin receptor},
  language     = {eng},
  month        = {12},
  number       = {11},
  pages        = {1404--1416},
  publisher    = {Elsevier},
  series       = {Free Radical Biology and Medicine},
  title        = {Red blood cells upregulate cytoprotective proteins and the labile iron pool in dividing human T cells despite a reduction in oxidative stress},
  url          = {http://dx.doi.org/10.1016/j.freeradbiomed.2003.08.011},
  volume       = {35},
  year         = {2003},
}