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鼻腔灌洗液和蛋白质组学作为识别刺激性环氧化学物质二甲基苄胺影响的手段。

Nasal lavage fluid and proteomics as means to identify the effects of the irritating epoxy chemical dimethylbenzylamine.

作者信息

Lindahl Mats, Irander Kristina, Tagesson Christer, Ståhlbom Bengt

机构信息

Division of Occupational and Environmental Medicine, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Sweden.

出版信息

Biomarkers. 2004 Jan-Feb;9(1):56-70. doi: 10.1080/13547500410001662005.

Abstract

The aims of this study were to describe the changes in the nasal lavage fluid (NLF) protein pattern after exposure to the irritating epoxy chemical dimethylbenzylamine (DMBA) and to identify the affected proteins using a proteomic approach. The protein patterns of NLF from six healthy subjects and eight epoxy workers with airway irritation were analysed using two-dimensional gel electrophoresis (2-DE) before and after exposure to 100 microg m(-3) DMBA for 2 h in an exposure chamber. NLF proteins were identified by (i) comparison with a 2-DE NLF reference database; (ii) N-terminal amino acid sequencing; and (iii) mass spectrometry. In NLF from healthy subjects, the levels of immunoglobulin A increased and the levels of Clara cell protein 16 (CC16) decreased after chamber exposure, while in NLF from epoxy workers, alpha(2)-macroglobulin and caeruloplasmin increased. Two previously unidentified proteins decreased in NLF from epoxy workers after exposure; these were identified as statherin and calgranulin B. In addition, the subjects who developed high counts of eosinophils in their nasal mucosa after chamber exposure had significantly lower levels of immunoglobulin-binding factor (IgBF) before exposure than subjects with low eosinophil infiltration. These results show that short-term exposure to DMBA causes distinct changes in NLF proteins. Moreover, three proteins that have previously not been associated with upper airway irritation were identified: statherin, calgranulin B and IgBF. Further studies are needed to investigate whether these proteins may be used as biomarkers of airway irritation and to give new insight into the ways in which occupational exposure to irritants causes inflammation of the airways.

摘要

本研究的目的是描述暴露于刺激性环氧化学物质二甲基苄胺(DMBA)后鼻灌洗液(NLF)蛋白质谱的变化,并使用蛋白质组学方法鉴定受影响的蛋白质。在暴露舱中,对6名健康受试者和8名有气道刺激症状的环氧工人在暴露于100μg m(-3) DMBA 2小时前后的NLF蛋白质谱进行二维凝胶电泳(2-DE)分析。通过以下方法鉴定NLF蛋白质:(i)与2-DE NLF参考数据库进行比较;(ii)N端氨基酸测序;(iii)质谱分析。在健康受试者的NLF中,暴露舱暴露后免疫球蛋白A水平升高,克拉拉细胞蛋白16(CC16)水平降低,而在环氧工人的NLF中,α2-巨球蛋白和铜蓝蛋白升高。暴露后,环氧工人的NLF中有两种先前未鉴定的蛋白质水平降低;这些蛋白质被鉴定为牙本质磷蛋白和钙粒蛋白B。此外,暴露舱暴露后鼻黏膜嗜酸性粒细胞计数高的受试者在暴露前免疫球蛋白结合因子(IgBF)水平明显低于嗜酸性粒细胞浸润低的受试者。这些结果表明,短期暴露于DMBA会导致NLF蛋白质发生明显变化。此外,还鉴定出三种先前与上呼吸道刺激无关的蛋白质:牙本质磷蛋白、钙粒蛋白B和IgBF。需要进一步研究以调查这些蛋白质是否可用作气道刺激的生物标志物,并为职业性接触刺激物导致气道炎症的方式提供新的见解。

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