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BackgroundAluminum (Al) is a lightweight metal that is widely present in the environment and the human body. It has been documented to cause various adverse health effects including the suppression of humoral immunity.ObjectiveTo investigate the role of oxidative stress in Al-induced humoral immunity suppression and to evaluate the possible protective effects of iron supplementation on this process.MethodsAdult C57BL/6J mice were exposed to Al at concentrations of 0, 200, or 800 μg·mL−1 via drinking water for three consecutive months. The expression of major histocompatibility complex class Ⅱ (I-A), proliferating cell markr-67 (Ki-67), and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) in splenic B cells was evaluated through flow cytometry. Splenic B cells from the mice treated with 800 μg·mL−1 Al or the control were sorted and treated in vitro with glutathione (GSH), N-Acetyl-L-cysteine (NAC), or a control vehicle. After 24 h, the expression of I-A was evaluated; and the hydroxyl radical (·OH)-generating potential, ·OH production, malondialdehyde (MDA) production, and iron content were assessed using commercial kits. Sixteen mice treated with 800 μg·mL−1 Al received an intravenous injection of either a ferric chloride solution containing 0.3 g·L−1 iron or a 0.9% sodium chloride solution, while eight control mice received 0.9% sodium chloride solution; the injection volume was 0.1 mL per mouse. Two and a half days after injection, I-A and Ki-67 expressions, ·OH-generating potential, ·OH production, and MDA production in splenic B cells were measured; and the concentrations of serum immunoglobulin (Ig) M and IgG were measured through (enzyme-linked immunosorbent assay) ELISA. The splenic B cells sorted from untreated mice were exposed to 0, 12.5, 25, or 50 μg·L−1 Al in vitro. The splenic B cells treated with 50 μg·L−1 Al and the splenic B cells sorted from 800 μg·mL−1 Al-treated mice were additionally treated with GSH and NAC in vitro. The iron supplementation groups, which included the 50 μg·L−1 Al-treated group and splenic B cells sorted from 800 μg·mL−1 Al-treated mice, were treated with a culture medium containing 30 μmol·L−1 iron in vitro. I-A and Ki-67 expressions, ·OH-generating potential, ·OH production, and MDA production in B cells were detected after a 24-h treatment period.ResultsIn the in vivo mouse model, exposure to 800 μg·mL−1 Al significantly inhibited the I-A and Ki-67 expressions (P<0.05), increased DCFH-DA expression and ·OH-generating potential (P<0.05, P<0.01), decreased iron content (P<0.01) and ·OH and MDA production (P<0.01, P<0.001) of splenic B cells, as well as serum IgM and IgG concentrations (P<0.05, P<0.01) in the mice. Exposure to 200 μg·mL−1 Al showed a tendency to decrease the I-A and Ki-67 expressions, and to increase the DCFH-DA expression in splenic B cells, but these differences were not significant. In the in vitro splenic B-cell model, Al (12.5, 25, and 50 μg·L−1) inhibited I-A and Ki-67 expressions (P<0.05, P<0.01) across all concentrations; 50 μg·L−1 Al increased the ·OH-generating potential (P<0.05), and decreased ·OH and MDA production (P<0.01, P<0.05) in B cells. Treatment with GSH and NAC further suppressed I-A expression (P<0.05) in B cells. Iron supplementation increased the ·OH and MDA production (P<0.05), restored I-A and Ki-67 expressions (P<0.05, P<0.01) in B cells, and elevated the serum IgM and IgG concentrations (P<0.05) in Al-treated mice.ConclusionAl suppresses humoral immunity and ·OH production in B cells. The underlying mechanism may involve the decreased iron content and the subsequent retardation of the Fenton reaction in B cells. Supplementing with iron can restore the Fenton reaction in B cells and potentially reverse Al-induced impairment of humoral immunity.
