Lewis T A, Hartmann C B, McCoy K L
Department of Microbiology and Immunology, Virginia Commonwealth University/Medical College of Virginia, Richmond 23298, USA.
J Immunol. 1998 Sep 1;161(5):2151-7.
Gallium arsenide (GaAs) is a semiconductor utilized in the electronics industry. Chemical exposure of animals causes a local inflammatory reaction, but systemic immunosuppression. Mice were administered i.p. 200 mg/kg GaAs crystals or latex beads, or vehicle. Five days after exposure, splenic macrophages were defective, whereas thioglycolate-elicited peritoneal macrophages (PEC) were more efficient in processing the Ag, pigeon cytochrome c, than vehicle control macrophages. Various aspects of the MHC class II Ag-processing pathway were examined. Both macrophage populations normally presented a peptide fragment to the CD4+ T cells. Surface MHC class II expression on the PEC was up-regulated, but splenic cells had normal MHC class II expression. PEC had elevated levels of glutathione and cysteine, major physiologic reducing thiols. However, the cysteine content of splenic macrophages was diminished. Proteolytic activities of aspartyl cathepsin D, and thiol cathepsins B and L were decreased significantly in splenic macrophages. On the other hand, thiol cathepsin activities were increased selectively in PEC. Latex bead-exposed PEC were not more potent APC, and their thiol cathepsin activities were unchanged, indicating that phagocytosis and nonspecific irritation were not responsible. The phenotype of PEC directly exposed to GaAs mirrored cytokine-activated macrophages, in contrast to splenic macrophages from a distant site. Therefore, GaAs exposure differentially modulated cathepsin activities in splenic macrophages and PEC, which correlated with their Ag-processing efficiency. Perhaps such distinct alterations may contribute to the local inflammation and systemic immunotoxicity caused by chemical exposure.
砷化镓（GaAs）是一种在电子工业中使用的半导体。动物接触化学物质会引发局部炎症反应，但会导致全身免疫抑制。给小鼠腹腔注射200mg/kg的砷化镓晶体或乳胶珠，或赋形剂。接触五天后，脾巨噬细胞存在缺陷，而巯基乙酸诱导的腹腔巨噬细胞（PEC）在处理抗原——鸽细胞色素c方面比赋形剂对照巨噬细胞更有效。对MHC II类抗原加工途径的各个方面进行了检查。两种巨噬细胞群体通常都会将肽片段呈递给CD4+ T细胞。PEC表面的MHC II类表达上调，但脾细胞的MHC II类表达正常。PEC中的谷胱甘肽和半胱氨酸水平升高，这是主要的生理性还原硫醇。然而，脾巨噬细胞中的半胱氨酸含量减少。脾巨噬细胞中天冬氨酸组织蛋白酶D以及巯基组织蛋白酶B和L的蛋白水解活性显著降低。另一方面，巯基组织蛋白酶活性在PEC中选择性增加。暴露于乳胶珠的PEC不是更强的抗原呈递细胞，其巯基组织蛋白酶活性没有变化，这表明吞噬作用和非特异性刺激不是原因所在。与远处部位的脾巨噬细胞相比，直接暴露于砷化镓的PEC的表型类似于细胞因子激活的巨噬细胞。因此，砷化镓暴露差异调节了脾巨噬细胞和PEC中的组织蛋白酶活性，这与它们的抗原加工效率相关。也许这种明显的改变可能导致化学物质暴露引起的局部炎症和全身免疫毒性。
