Human Macrophages Constitute Targets for Immunotoxic Inorganic Arsenic

摘要: Chronic exposure to inorganic arsenic, a widely distributed environmental contaminant, can lead toxic effects, including immunosuppression. Owing the established roles of human macrophages in immune defense, we determined, present study, whether arsenic affect these major cells. Our results demonstrate that noncytotoxic concentrations trioxide (As2O3), an trivalent form, markedly impair differentiated features blood monocyte-derived macrophages. First, treatment with 1 microM As2O3 induced rapid cell rounding and subsequent loss adhesion. These morphologic alterations were associated marked reorganization actin cytoskeleton, which includes retraction peripheral extensions formation cortical ring. In addition, reduced expression various macrophagic surface markers, enhanced monocytic marker CD14, altered both endocytosis phagocytosis; unexpectedly, metalloid also strongly potentiated TNFalpha IL-8 by LPS. Finally, like monocytes, As2O3-treated be into dendritic-like Impairment macrophage function mainly resulted from activation RhoA/Rho-associated kinase pathway; indeed, pretreatment Rho-associated inhibitor Y-27632 prevented effects on cytoskeleton phagocytosis. Moreover, was found increase level active GTP-bound form RhoA phosphorylated-Moesin, adaptor protein involved regulation. Taken together, our demonstrated constitute sensitive targets may contribute immunotoxicity this contaminant.