期刊
TOXICOLOGY IN VITRO
卷 27, 期 3, 页码 1018-1024出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2013.01.018
关键词
Antigen presenting cell; Autophagy; MIIC exocytosis; MHC-II; Endosomal trafficking
类别
Aberrant major histocompatibility complex class II (MHC-II) surface expression on antigen presenting cells (APCs) is associated with dysregulated immune homeostasis. Lead (Pb) is known to increase MHC-II surface expression on murine peritoneal macrophages ex vivo at concentrations exceeding 25 mu M. Little data exist examining this effect at physiologically relevant concentrations. To address this deficit, we examined the effects of Pb on MHC-II surface expression, secondary T-cell activation markers (CD80, CD86, CD40), cell viability, cellular metabolic activity, and beta-hexosaminidase activity in RAW 267.4 macrophage cell lines, with changes in cell ultrastructure evaluated by electron and confocal microscopy. Pb induced an increase in MHC-II, CD86, and lysosome-associated LAMP-1 and LAMP-2 surface mean expression during one doubling cycle (17 h), which was mirrored by increased beta-hexosaminidase activity. Although cell viability was unaffected, cellular metabolism was inhibited. Electron microscopy revealed evidence of lipid vacuolization, macroautophagy and myelin figure formation in cells cultured with either Pb or LPS. Confocal microscopy with antibodies against LC3B showed a punctate pattern consistent with the presence of mature autophagosomes. Collectively, these data suggest that 2.5-5.0 mu M Pb increased MHC-II surface expression by inhibiting metabolic activity, inducing autophagy, and increasing MHC-II trafficking in a macrophage cell line. (C) 2013 Elsevier Ltd. All rights reserved.
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