Induction of lupus-related specific autoantibodies by non-specific inflammation caused by an intraperitoneal injection of n-hexadecane in BALB/c mice
Induction of lupus-related specific autoantibodies by non-specific inflammation caused by an intraperitoneal injection of n-hexadecane in BALB/c mice
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DOI：
10.1016/j.tox.2005.10.011
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发表时间：
2006-02-01
期刊：
影响因子：
4.5
通讯作者：
Satoh, M
中科院分区：
文献类型：
--
作者：
Kuroda, Y;Ono, N;Satoh, M
单次腹膜内（i. p.）注射降植烷、不完全弗氏佐剂（IFA）或佐剂油角鲨烯，但不注射高分子量药用矿物油，在非自身免疫品系的小鼠中诱导针对nRNP/Sm和-Su的狼疮相关自身抗体。这种能力似乎与碳氢化合物的低分子量和佐剂性有关。石油中存在的正十六烷（C16 H34）具有佐剂活性，并像其他诱发狼疮的油一样诱发啮齿动物的关节炎。除了从饮食中接触矿物油中的正十六烷外，还可通过吸入油雾、喷气燃料或柴油机废气或通过皮肤吸收而接触。由于正十六烷是一种低分子量的佐剂烃油，类似于其他狼疮诱导烃，本研究检查了它是否也可以诱导小鼠狼疮相关的自身抗体。雌性BALB/cJ小鼠接受单次腹膜内注射0.5 ml正十六烷、降植烷或盐水（对照）。3个月后进行病理学和血清学检查（免疫球蛋白水平，免疫荧光，免疫沉淀和ELISA的自身抗体）。出乎意料的是，所有正十六烷治疗的小鼠，但没有在其他组，在2.5个月内发展炎性腹水。正十六烷诱导高γ球蛋白血症（IgG 1，IgG 2a）、抗核抗体（滴度> 1：160，67%）和抗胞浆抗体（58%）以及针对nRNP/Sm（25%）、Su（33%）、ssDNA（83%）和染色质（100%）的自身抗体。因此，由正十六烷引起的非特异性炎症导致产生一组有限的特异性自身抗体。这些以前未被认识到的正十六烷的免疫学效应可能有影响，在监测人类暴露于碳氢化合物和自身免疫性疾病的发病机制。(C)2005爱思唯尔爱尔兰有限公司保留所有权利。
A single intraperitoneal (i.p.) injection of pristane, incomplete Freund's adjuvant (IFA), or the adjuvant oil squalene, but not high molecular weight medicinal mineral oils, induces lupus-related autoantibodies to nRNP/Sm and -Su in non-autoimmune strains of mice. This ability appears to be associated with the low molecular weight and adjuvanticity of hydrocarbon.n-Hexadecane (C16H34), which is present in petroleum, has adjuvant activity and induces arthritis in rodents like other lupus-inducing oils. In addition to dietary exposure to n-hexadecane in mineral oils, exposure also occurs via inhalation of oil mist, jet fuel, or diesel exhaust or by absorption through the skin. Since n-hexadecane is a low molecular weight adjuvant hydrocarbon oil similar to other lupus-inducing hydrocarbons, the present study examined whether it can also induce lupus-related autoantibodies in mice. Female BALB/cJ mice received a single i.p. injection of 0.5 nil of n-hexadecane, pristane, or saline (control). Pathology and serology (immunoglobulin levels, autoantibodies by immunofluorescence, immunoprecipitation, and ELISA) were examined 3 months later. Unexpectedly, all n-hexadecane-treated mice, but none in the other groups, developed inflammatory ascites within 2.5 months. n-Hexadecane induced hypergammaglobulinemia (IgG1, IgG2a), antinuclear (titer> 1:160, 67%) and -cytoplasmic antibodies (58%) and autoantibodies to nRNP/Sm (25%), Su (33%), ssDNA (83%), and chromatin (100%). Therefore, non-specific inflammation caused by n-hexadecane resulted in the production of a limited set of specific autoantibodies. These previously unrecognized immunological effects of n-hexadecane may have implications in monitoring human exposure to hydrocarbons and in the pathogenesis of autoimmune diseases. (C) 2005 Elsevier Ireland Ltd. All rights reserved.