Klan M J, Adams D O, Lewis J G
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
Toxicol Appl Pharmacol. 1990 Apr;103(2):198-205. doi: 10.1016/0041-008x(90)90222-g.
Exposure to benzene has been shown to decrease resistance to challenges by Listeria monocytogenes or tumor cells in mice. Alterations of T-lymphocytes have been suggested as one probable cause. Macrophages are also critical participants in resistance to Listeria and to tumor cells. We have previously shown that exposure of macrophages in vitro to benzene metabolites, but not to benzene, inhibited several functions of macrophages that are critical for host resistance. The present studies were conducted to determine the effects of exposure to benzene in vivo on the murine mononuclear phagocyte system. Treated animals received daily subcutaneous injections of benzene (800 mg/kg) for 5 days. Macrophages were obtained by lavage from the peritoneal cavity after ip injection of sterile eliciting agents. Enumeration, peroxidase histochemistry, and a series of functional assays were performed. Animals exposed to benzene displayed a decreased number of macrophages elicited by peptone injection. Specific alterations of macrophage functions included a 50% decrease of Fc-receptor-mediated phagocytosis and 70% inhibition of tumor cell cytolysis but an enhancement of TPA-stimulated H2O2 release. There was no effect on interferon-gamma stimulated expression of Ia antigen. The observations that the elicited macrophage populations were composed of newly immigrated cells and that benzene treatment was terminated 3 days before the functional analyses were performed suggest that benzene was affecting monocytes in the blood and precursor cells in the bone marrow. Alterations of macrophage functions in injection controls suggested that determining the primary effect of exposure to benzene may be complicated by the inflammation induced by treatment at the site of injection.(ABSTRACT TRUNCATED AT 250 WORDS)
已表明,小鼠接触苯会降低其对单核细胞增生李斯特菌或肿瘤细胞攻击的抵抗力。T淋巴细胞的改变被认为是一个可能原因。巨噬细胞也是抵抗李斯特菌和肿瘤细胞的关键参与者。我们之前已表明,体外将巨噬细胞暴露于苯代谢物而非苯,会抑制巨噬细胞对宿主抵抗力至关重要的几种功能。本研究旨在确定体内接触苯对小鼠单核吞噬细胞系统的影响。受试动物每天皮下注射苯(800毫克/千克),共5天。腹腔注射无菌诱导剂后,通过腹腔灌洗获取巨噬细胞。进行了细胞计数、过氧化物酶组织化学及一系列功能测定。接触苯的动物经蛋白胨注射诱导出的巨噬细胞数量减少。巨噬细胞功能的具体改变包括Fc受体介导的吞噬作用降低50%,肿瘤细胞溶解抑制70%,但佛波酯刺激的过氧化氢释放增强。对干扰素-γ刺激的Ia抗原表达无影响。诱导的巨噬细胞群体由新迁入的细胞组成,且在进行功能分析前3天终止苯处理,这些观察结果表明苯正在影响血液中的单核细胞和骨髓中的前体细胞。注射对照中巨噬细胞功能的改变表明,确定接触苯的主要影响可能因注射部位处理引起的炎症而变得复杂。(摘要截短于250词)