Arsenite selectively inhibits mouse bone marrow lymphoid progenitor cell development in vivo and in vitro and suppresses humoral immunity in vivo.
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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.
