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.
(Less)
- author
- Fonseca, Ana Mafalda
; Pereira, Carlos F.
LU
; Porto, Graça
and Arosa, Fernando A.
- publishing date
- 2003-12-01
- 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
-
- pmid:14642388
- 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
- 2025-05-27 08:48:52
@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}},
keywords = {{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}},
doi = {{10.1016/j.freeradbiomed.2003.08.011}},
volume = {{35}},
year = {{2003}},
}