Department of Pharmacology and Experimental Therapeutics, The Hebrew University of Jerusalem, Israel.
Allergy. 2010 Feb;65(2):168-74. doi: 10.1111/j.1398-9995.2009.02148.x. Epub 2009 Oct 5.
Eosinophils are critically involved in allergic inflammation and tissue remodeling. Osteopontin (OPN) is a glycoprotein molecule which exhibits pro-fibrogenic and pro-angiogenic properties and has recently also been implicated in allergic diseases. In this study, we investigated the expression and function of OPN in human eosinophils.
Osteopontin mRNA (RT-PCR) and protein (immunofluorescence) expression in peripheral blood eosinophils from atopic human subjects were evaluated. Soluble OPN release was determined in resting and activated eosinophils. The contribution of OPN to eosinophil-induced angiogenesis was determined using the chick embryo chorio- allantoic membrane (CAM) assay and OPN-induced eosinophil chemotaxis was determined (ChemoTx System microplate wells). Finally, OPN expression in bronchoalveolar lavage (BAL) fluids from mild asthmatic and normal control subjects was determined.
Osteopontin is expressed in human eosinophils and is increased following GM-CSF and IL-5 activation. Eosinophil-derived OPN contributes to eosinophil-induced angiogenesis. Recombinant OPN promotes eosinophil chemotaxis in vitro and this effect is mediated by alpha(4)beta(1) integrin binding. Soluble OPN is increased in the bronchoalveolar lavage fluid from mild asthmatic subjects and correlates with eosinophil counts.
We therefore conclude that OPN is likely to contribute to the process of angiogenesis observed in the airways in asthma.
嗜酸性粒细胞在过敏炎症和组织重塑中起着关键作用。骨桥蛋白(OPN)是一种糖蛋白分子,具有促纤维化和促血管生成特性,最近也与过敏疾病有关。在这项研究中,我们研究了 OPN 在人嗜酸性粒细胞中的表达和功能。
评估了来自特应性人类受试者外周血嗜酸性粒细胞中的 OPN mRNA(RT-PCR)和蛋白(免疫荧光)表达。测定了静止和激活的嗜酸性粒细胞中可溶性 OPN 的释放。通过鸡胚绒毛尿囊膜(CAM)测定法确定 OPN 对嗜酸性粒细胞诱导的血管生成的贡献,并通过 OPN 诱导的嗜酸性粒细胞趋化性测定(ChemoTx 系统微孔板孔)来确定 OPN 诱导的嗜酸性粒细胞趋化性。最后,测定了轻度哮喘和正常对照受试者支气管肺泡灌洗液(BAL)中 OPN 的表达。
OPN 在人嗜酸性粒细胞中表达,并在 GM-CSF 和 IL-5 激活后增加。嗜酸性粒细胞衍生的 OPN 有助于嗜酸性粒细胞诱导的血管生成。重组 OPN 在体外促进嗜酸性粒细胞趋化,这种作用是通过 alpha(4)beta(1)整合素结合介导的。轻度哮喘患者支气管肺泡灌洗液中的可溶性 OPN 增加,并与嗜酸性粒细胞计数相关。
因此,我们得出结论,OPN 可能有助于哮喘气道中观察到的血管生成过程。