Respiratory Medicine & Allergology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
Respiratory Medicine & Allergology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
J Cyst Fibros. 2015 Jul;14(4):453-63. doi: 10.1016/j.jcf.2014.11.010. Epub 2014 Dec 6.
The glycoprotein osteopontin plays important roles in several states of disease associated with inflammation, for example by recruiting neutrophils but its expression and possible roles in cystic fibrosis (CF) have not been investigated.
Immunohistochemistry and ELISA were used to detect osteopontin in clinical samples. In addition, osteopontin-binding and functional interference with antibacterial (ELR-negative) and neutrophil-recruiting (ELR-positive) CXC-chemokines were investigated using in vitro assays.
Increased osteopontin-expression was found in the airways of CF patients compared with controls. Interestingly, osteopontin bound to ELR-negative CXC-chemokines, reducing their antibacterial and receptor-activating properties while no binding or interference with the function of ELR-positive chemokines was found.
High expression of osteopontin is likely part of the dysregulated inflammation seen in CF, impairing the activities of ELR-negative chemokines that both serve as innate antibiotics and recruit NK and cytotoxic T cells, instead promoting an excessive influx of neutrophils, and may thus contribute to disease progress.
糖蛋白骨桥蛋白在与炎症相关的几种疾病状态中发挥着重要作用，例如通过招募中性粒细胞，但它在囊性纤维化 (CF) 中的表达和可能的作用尚未得到研究。
免疫组织化学和 ELISA 用于检测临床样本中的骨桥蛋白。此外，还使用体外测定法研究了骨桥蛋白与抗菌（无 ELR）和中性粒细胞募集（有 ELR）CXC 趋化因子的结合和功能干扰。
与对照组相比，CF 患者的气道中发现骨桥蛋白表达增加。有趣的是，骨桥蛋白与无 ELR 的 CXC 趋化因子结合，降低了它们的抗菌和受体激活特性，而没有发现与 ELR 阳性趋化因子的结合或干扰。
骨桥蛋白的高表达可能是 CF 中失调的炎症的一部分，削弱了作为先天抗生素并招募 NK 和细胞毒性 T 细胞的无 ELR 趋化因子的活性，反而促进了中性粒细胞的过度涌入，并可能因此促进疾病进展。
