Arsenite selectively inhibits mouse bone marrow lymphoid progenitor cell development in vivo and in vitro and suppresses humoral immunity in vivo.
It is known that exposure to As(+3) via drinking water causes a disruption of the immune system and significantly compromises the immune response to infection. The purpose of these studies was to assess the effects of As(+3) on bone marrow progenitor cell colony formation and the humoral immune resp...
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doaj-f5df3644b82b43839de87ca3bc7e10642020-11-25T01:24:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9392010.1371/journal.pone.0093920Arsenite selectively inhibits mouse bone marrow lymphoid progenitor cell development in vivo and in vitro and suppresses humoral immunity in vivo.Peace C EzehFredine T LauerDebra MacKenzieShea McClainKe Jian LiuLaurie G HudsonA Jay GandolfiScott W BurchielIt is known that exposure to As(+3) via drinking water causes a disruption of the immune system and significantly compromises the immune response to infection. The purpose of these studies was to assess the effects of As(+3) on bone marrow progenitor cell colony formation and the humoral immune response to a T-dependent antigen response (TDAR) in vivo. In a 30 day drinking water study, mice were exposed to 19, 75, or 300 ppb As(+3). There was a decrease in bone marrow cell recovery, but not spleen cell recovery at 300 ppb As(+3). In the bone marrow, As(+3) altered neither the expression of CD34+ and CD38+ cells, markers of early hematopoietic stem cells, nor CD45-/CD105+, markers of mesenchymal stem cells. Spleen cell surface marker CD45 expression on B cells (CD19+), T cells (CD3+), T helper cells (CD4+) and cytotoxic T cells (CD8+), natural killer (NK+), and macrophages (Mac 1+) were not altered by the 30 day in vivo As(+3) exposure. Functional assays of CFU-B colony formation showed significant selective suppression (p<0.05) by 300 ppb As(+3) exposure, whereas CFU-GM formation was not altered. The TDAR of the spleen cells was significantly suppressed at 75 and 300 ppb As(+3). In vitro studies of the bone marrow revealed a selective suppression of CFU-B by 50 nM As(+3) in the absence of apparent cytotoxicity. Monomethylarsonous acid (MMA(+3)) demonstrated a dose-dependent and selective suppression of CFU-B beginning at 5 nM (p<0.05). MMA(+3) suppressed CFU-GM formation at 500 nM, a concentration that proved to be nonspecifically cytotoxic. As(+5) did not suppress CFU-B and/or CFU-GM in vitro at concentrations up to 500 nM. Collectively, these results demonstrate that As(+3) and likely its metabolite (MMA(+3)) target lymphoid progenitor cells in mouse bone marrow and mature B and T cell activity in the spleen.http://europepmc.org/articles/PMC3979857?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Peace C Ezeh Fredine T Lauer Debra MacKenzie Shea McClain Ke Jian Liu Laurie G Hudson A Jay Gandolfi Scott W Burchiel |
spellingShingle |
Peace C Ezeh Fredine T Lauer Debra MacKenzie Shea McClain Ke Jian Liu Laurie G Hudson A Jay Gandolfi Scott W Burchiel Arsenite selectively inhibits mouse bone marrow lymphoid progenitor cell development in vivo and in vitro and suppresses humoral immunity in vivo. PLoS ONE |
author_facet |
Peace C Ezeh Fredine T Lauer Debra MacKenzie Shea McClain Ke Jian Liu Laurie G Hudson A Jay Gandolfi Scott W Burchiel |
author_sort |
Peace C Ezeh |
title |
Arsenite selectively inhibits mouse bone marrow lymphoid progenitor cell development in vivo and in vitro and suppresses humoral immunity in vivo. |
title_short |
Arsenite selectively inhibits mouse bone marrow lymphoid progenitor cell development in vivo and in vitro and suppresses humoral immunity in vivo. |
title_full |
Arsenite selectively inhibits mouse bone marrow lymphoid progenitor cell development in vivo and in vitro and suppresses humoral immunity in vivo. |
title_fullStr |
Arsenite selectively inhibits mouse bone marrow lymphoid progenitor cell development in vivo and in vitro and suppresses humoral immunity in vivo. |
title_full_unstemmed |
Arsenite selectively inhibits mouse bone marrow lymphoid progenitor cell development in vivo and in vitro and suppresses humoral immunity in vivo. |
title_sort |
arsenite selectively inhibits mouse bone marrow lymphoid progenitor cell development in vivo and in vitro and suppresses humoral immunity in vivo. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
It is known that exposure to As(+3) via drinking water causes a disruption of the immune system and significantly compromises the immune response to infection. The purpose of these studies was to assess the effects of As(+3) on bone marrow progenitor cell colony formation and the humoral immune response to a T-dependent antigen response (TDAR) in vivo. In a 30 day drinking water study, mice were exposed to 19, 75, or 300 ppb As(+3). There was a decrease in bone marrow cell recovery, but not spleen cell recovery at 300 ppb As(+3). In the bone marrow, As(+3) altered neither the expression of CD34+ and CD38+ cells, markers of early hematopoietic stem cells, nor CD45-/CD105+, markers of mesenchymal stem cells. Spleen cell surface marker CD45 expression on B cells (CD19+), T cells (CD3+), T helper cells (CD4+) and cytotoxic T cells (CD8+), natural killer (NK+), and macrophages (Mac 1+) were not altered by the 30 day in vivo As(+3) exposure. Functional assays of CFU-B colony formation showed significant selective suppression (p<0.05) by 300 ppb As(+3) exposure, whereas CFU-GM formation was not altered. The TDAR of the spleen cells was significantly suppressed at 75 and 300 ppb As(+3). In vitro studies of the bone marrow revealed a selective suppression of CFU-B by 50 nM As(+3) in the absence of apparent cytotoxicity. Monomethylarsonous acid (MMA(+3)) demonstrated a dose-dependent and selective suppression of CFU-B beginning at 5 nM (p<0.05). MMA(+3) suppressed CFU-GM formation at 500 nM, a concentration that proved to be nonspecifically cytotoxic. As(+5) did not suppress CFU-B and/or CFU-GM in vitro at concentrations up to 500 nM. Collectively, these results demonstrate that As(+3) and likely its metabolite (MMA(+3)) target lymphoid progenitor cells in mouse bone marrow and mature B and T cell activity in the spleen. |
url |
http://europepmc.org/articles/PMC3979857?pdf=render |
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