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在棕色挪威大鼠和Wistar大鼠经皮应用致敏和非致敏化学物质后,局部淋巴结激活及IgE反应。

Local lymph node activation and IgE responses in brown Norway and Wistar rats after dermal application of sensitizing and non-sensitizing chemicals.

作者信息

Arts J H, Dröge S C, Spanhaak S, Bloksma N, Penninks A H, Kuper C F

机构信息

TNO Nutrition and Food Research Institute, Toxicology Division, Zeist, The Netherlands.

出版信息

Toxicology. 1997 Feb 28;117(2-3):229-34. doi: 10.1016/s0300-483x(96)03576-7.

Abstract

The local lymph node assay (LLNA) and the IgE test in the mouse are proposed models for predictive recognition of low molecular weight chemicals causing IgE-mediated allergic airway reactions in man. Since rats are commonly used in routine toxicity studies and a previous study (Arts et al. (1996) Food Chem. Toxicol. 34, 55-62) has shown that several rat strains were found appropriate for the LLNA, the suitability of the rat for the IgE test was examined in the present study. Serum IgE concentrations were examined following topical exposure of Brown Norway (BN) and Wistar rats to each of four chemicals with known diverse sensitization potential in humans: trimellitic anhydride (TMA), a dermal and respiratory sensitizer, dinitrochlorobenzene (DNCB), a dermal sensitizer with no or limited potential to cause respiratory allergy; formaldehyde (FA), a skin irritant and dermal sensitizer with equivocal evidence for respiratory sensitizing potential; methyl salicylate (MS), a skin irritant devoid of sensitizing properties. Of the four tested chemicals, only exposure to TMA resulted in a significant increase in serum IgE concentration and this response was only evoked in the high-IgE-responding BN rat. The latter two chemicals were also tested for lymph node activation, in casu the ear-draining lymph nodes. FA caused a dose-dependent activation of the draining lymph nodes whereas MS was inactive. The results as obtained with TMA, DNCB and MS in the rat are in agreement with human data. The results with FA though, indicate the need for further studies of chemicals that have both irritant and sensitizing properties at about similar concentrations or may act through non-IgE-mediated immune mechanisms.

摘要

局部淋巴结试验(LLNA)和小鼠IgE试验被认为是预测识别可导致人类IgE介导的过敏性气道反应的低分子量化学物质的模型。由于大鼠常用于常规毒性研究,且先前的一项研究(Arts等人,(1996年)《食品化学毒理学》34卷,55 - 62页)表明几种大鼠品系适用于LLNA,因此在本研究中检测了大鼠对IgE试验的适用性。在棕色挪威(BN)大鼠和Wistar大鼠经皮暴露于四种在人类中具有不同致敏潜力的已知化学物质后,检测血清IgE浓度:偏苯三酸酐(TMA),一种皮肤和呼吸道致敏剂;二硝基氯苯(DNCB),一种无或仅有有限呼吸道过敏潜力的皮肤致敏剂;甲醛(FA),一种皮肤刺激物和皮肤致敏剂,其呼吸道致敏潜力证据不明确;水杨酸甲酯(MS),一种无致敏特性的皮肤刺激物。在四种受试化学物质中,只有暴露于TMA导致血清IgE浓度显著增加,且这种反应仅在高IgE反应的BN大鼠中诱发。还对后两种化学物质进行了淋巴结激活检测,具体是耳引流淋巴结。FA导致引流淋巴结呈剂量依赖性激活,而MS无活性。大鼠中TMA、DNCB和MS的结果与人类数据一致。不过,FA的结果表明需要对在大约相似浓度下具有刺激和致敏特性或可能通过非IgE介导的免疫机制起作用的化学物质进行进一步研究。

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