Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells
Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells
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DOI：
10.1136/ard.2007.075192
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发表时间：
2008-10-01
影响因子：
27.4
通讯作者：
Catrina, A. I.
中科院分区：
文献类型：
--
作者：
Makrygiannakis, D.;Hermansson, M.;Catrina, A. I.
目的：抗环瓜氨酸肽抗体阳性的类风湿关节炎（RA）中HLA-DR共享表位基因与吸烟之间存在基因-环境相互作用。吸烟者的支气管肺泡灌洗（BAL）细胞中的瓜氨酸化蛋白的鉴定已导致的建议，吸烟引起的瓜氨酸可能是第一步的致病链RA.Objective：To confirm and extend these findings.Methods：免疫组化进行BAL细胞和支气管粘膜活检切片通过支气管镜从14个健康吸烟者和16个健康的非吸烟者。两种抗体识别瓜氨酸蛋白，两种抗体识别肽基精氨酸脱亚胺酶（PAD）2酶和一个识别PAD 4 enzymes.Results：瓜氨酸蛋白上调BAL细胞的健康吸烟者相比，健康的非吸烟者。这与PAD 2酶的较高表达有关。相同水平的瓜氨酸蛋白存在于支气管粘膜活检标本的健康吸烟者和非吸烟者，尽管较高的表达的PAD 2在smokers.Conclusion：这项研究提供了证据表明，吸烟增强PAD 2的表达在支气管粘膜和肺泡隔室，随之产生的瓜氨酸蛋白在后者。吸烟是一种环境因素，可能导致遗传易感受试者产生瓜氨酸自身免疫。
Objectives: A gene-environment interaction between HLA-DR shared epitope genes and smoking in anti-cyclic citrullinated peptide antibody-positive rheumatoid arthritis (RA) has been reported. Identification of citrullinated proteins in bronchoalveolar lavage (BAL) cells from smokers has led to the suggestion that citrullination induced by smoking might be the first step in the pathogenic chain of RA.Objective: To confirm and extend these findings.Methods: Immunohistochemistry was performed on BAL cells and bronchial mucosal biopsy sections obtained through bronchoscopy from 14 healthy smokers and 16 healthy non-smokers. Two antibodies recognising citrullinated proteins, two antibodies recognising peptidylarginine deiminase (PAD) 2 enzyme and one recognising PAD4 enzyme were used.Results: Citrullinated proteins are upregulated in BAL cells of healthy smokers compared with healthy nonsmokers. This was associated with higher expression of the PAD2 enzyme. The same level of citrullinated proteins was present in bronchial mucosal biopsy specimens of healthy smokers and non-smokers, despite higher expression of PAD2 in smokers.Conclusion: This study provides evidence that smoking enhances PAD2 expression in the bronchial mucosal and alveolar compartment, with consequent generation of citrullinated proteins in the latter. Smoking is an environmental factor that may lead to citrulline auto-immunity in genetically susceptible subjects.