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大鼠亚急性暴露于氧化三丁基锡后的免疫改变。

Immune alterations in rats following subacute exposure to tributyltin oxide.

作者信息

Smialowicz R J, Riddle M M, Rogers R R, Leubke R W, Copeland C B, Ernst G G

机构信息

Pulmonary Toxicology Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.

出版信息

Toxicology. 1990 Nov;64(2):169-78. doi: 10.1016/0300-483x(90)90133-2.

Abstract

Adult male Fischer 344 rats were dosed by oral gavage with bis(tri-n-butyltin)oxide (TBTO) in peanut oil for 10 consecutive days, at dosages ranging from 1.25 to 15 mg/kg/day. Other groups of rats were dosed daily for 10 days by oral gavage with cyclophosphamide (CY) at dosages ranging from 0.75 to 6 mg/kg/day. These rats served as positive controls for the immune assays employed. The immune function parameters examined included the following: delayed-type hypersensitivity (DTH) and antibody responses to bovine serum albumin (BSA), primary antibody responses to sheep red blood cells (SRBC) and trinitrophenyl lipopolysaccharide (TNP-LPS) and enumeration of splenic lymphocyte populations. The DTH and antibody responses to BSA were not affected by TBTO exposure; however these responses were suppressed in rats dosed with CY at 6 mg/kg/day. The plaque forming cell (PFC) response to the T cell-dependent antigen SRBC was enhanced in rats dosed with TBTO at from 5 to 15 mg/kg/day. On the other hand, the PFC response to the T cell-independent antigen TNP-LPS was unaffected by TBTO exposure. Rats dosed with CY had suppressed PFC responses to SRBC and TNP-LPS at dosages of 3 and 6 mg/kg/day, respectively. Enumeration of splenic lymphocyte populations from TBTO-exposed rats revealed a reduction in OX8- but not W3/25- or IgG-positive cells. These results, as well as results from an earlier study from this lab, suggest that T lymphocytes are a primary target for TBTO-induced immune alterations and that the enhancement of the PFC response to SRBC in TBTO-exposed rats may be mediated by alterations in the suppressor (OX8-positive) T lymphocyte population.

摘要

成年雄性Fischer 344大鼠连续10天经口灌胃给予花生油中的双(三正丁基锡)氧化物(TBTO),剂量范围为1.25至15毫克/千克/天。其他几组大鼠连续10天经口灌胃给予环磷酰胺(CY),剂量范围为0.75至6毫克/千克/天。这些大鼠用作所采用免疫测定的阳性对照。所检测的免疫功能参数包括:迟发型超敏反应(DTH)以及对牛血清白蛋白(BSA)的抗体反应、对绵羊红细胞(SRBC)和三硝基苯基脂多糖(TNP-LPS)的初次抗体反应以及脾淋巴细胞群体计数。对BSA的DTH和抗体反应不受TBTO暴露的影响;然而,在给予6毫克/千克/天CY的大鼠中这些反应受到抑制。在给予5至15毫克/千克/天TBTO的大鼠中,对T细胞依赖性抗原SRBC的空斑形成细胞(PFC)反应增强。另一方面,对T细胞非依赖性抗原TNP-LPS的PFC反应不受TBTO暴露的影响。给予CY的大鼠在3和6毫克/千克/天的剂量下,对SRBC和TNP-LPS的PFC反应分别受到抑制。对TBTO暴露大鼠的脾淋巴细胞群体计数显示,OX8阳性细胞减少,但W3/25或IgG阳性细胞未减少。这些结果以及本实验室早期研究的结果表明,T淋巴细胞是TBTO诱导免疫改变的主要靶点,并且在TBTO暴露大鼠中对SRBC的PFC反应增强可能由抑制性(OX8阳性)T淋巴细胞群体的改变介导。

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