Takahashi A, Kurokawa M, Konno S, Ito K, Kon S, Ashino S, Nishimura T, Uede T, Hizawa N, Huang S-K, Nishimura M
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Hokkaido, Japan.
Clin Exp Allergy. 2009 Aug;39(8):1152-9. doi: 10.1111/j.1365-2222.2009.03249.x. Epub 2009 Apr 23.
Osteopontin (OPN) is an extracellular matrix protein with a wide range of functions, and is involved in various inflammatory diseases. However, the role of OPN in eosinophilic airway inflammation is unclear.
To elucidate the role of OPN in eosinophilic airway inflammation.
OPN protein levels in induced sputum from asthmatic patients and healthy controls were measured. Eosinophil migration assays were performed in the presence or absence of OPN, a blocking antibody (Ab) recognizing its integrin-binding domain (2K1) and an anti-integrin alpha 4 Ab (P1H4). In the mouse asthma model, the levels of eosinophilia were examined in bronchoalveolar lavage fluids (BALFs) from ovalbumin (OVA)-sensitized and -challenged mice with or without administration of an Ab (M5) corresponding to human 2K1.
Levels of OPN in induced sputum were significantly higher in asthmatic patients when compared with healthy controls. In addition, levels of OPN were correlated with the percentage of sputum eosinophils. OPN induced significant migration of human eosinophils and this effect was inhibited by 2K1 and P1H4. M5 significantly attenuated OVA-induced eosinophilia in BALFs.
These results indicate that OPN plays a role in the migration of eosinophils into the airways and may be involved in the pathogenesis of asthma.
骨桥蛋白(OPN)是一种具有多种功能的细胞外基质蛋白,参与多种炎症性疾病。然而,OPN在嗜酸性粒细胞气道炎症中的作用尚不清楚。
阐明OPN在嗜酸性粒细胞气道炎症中的作用。
检测哮喘患者和健康对照者诱导痰中OPN蛋白水平。在有或无OPN、识别其整合素结合域的阻断抗体(Ab)(2K1)和抗整合素α4抗体(P1H4)存在的情况下进行嗜酸性粒细胞迁移试验。在小鼠哮喘模型中,检测卵清蛋白(OVA)致敏和激发的小鼠在给予或不给予与人2K1对应的抗体(M5)时支气管肺泡灌洗液(BALF)中的嗜酸性粒细胞水平。
与健康对照相比,哮喘患者诱导痰中OPN水平显著升高。此外,OPN水平与痰中嗜酸性粒细胞百分比相关。OPN诱导人嗜酸性粒细胞显著迁移,这种作用被2K1和P1H4抑制。M5显著减轻OVA诱导的BALF中嗜酸性粒细胞增多。
这些结果表明,OPN在嗜酸性粒细胞向气道的迁移中起作用,可能参与哮喘的发病机制。