Lane Andrew P, Truong-Tran Quynh-Ai, Myers Allan, Bickel Carol, Schleimer Robert P
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins, University School of Medicine, Baltimore, Maryland, USA.
Am J Rhinol. 2006 Jan-Feb;20(1):117-23.
There is a growing appreciation of the role that nasal mucosa plays in innate immunity. In this study, the expression of pattern recognition receptors known as toll-like receptors (TLRs) and the effector molecules complement factor 3 (C3), properdin, and serum amyloid A (SAA) were examined in human sinonasal mucosa obtained from control subjects and patients with chronic rhinosinusitis (CRS).
Sinonasal mucosal specimens were obtained from 20 patients with CRS and 5 control subjects. Messenger RNA (mRNA) was isolated and tested using Taqman real-time polymerase chain reaction with primer and probe sets for C3, complement factor P, and SAA. Standard polymerase chain reaction was performed for the 10 known TLRs. Immunohistochemistry was performed on the microscopic sections using antibodies against C3.
Analysis of the sinonasal sample mRNA revealed expression of all 10 TLRs in both CRS samples and in control specimens. Expression of the three effector proteins was detected also, with the levels of mRNA for C3 generally greater than SAA and properdin in CRS patients. No significant differences were found in TLR or innate immune protein expression in normal controls. Immunohistochemical analysis of sinonasal mucosal specimens established C3 staining ranging from 20 to 85% of the epithelium present.
These studies indicate that sinonasal mucosa expresses genes involved in innate immunity including the TLRs and proteins involved in complement activation. We hypothesize that local production of complement and acute phase proteins by airway epithelium on stimulation of innate immune receptors may play an important role in host defense in the airway and, potentially, in the pathogenesis of CRS.
鼻黏膜在固有免疫中所起的作用日益受到重视。在本研究中,我们检测了从对照受试者和慢性鼻 - 鼻窦炎(CRS)患者获取的人鼻窦黏膜中,名为Toll样受体(TLRs)的模式识别受体以及效应分子补体因子3(C3)、备解素和血清淀粉样蛋白A(SAA)的表达情况。
从20例CRS患者和5名对照受试者获取鼻窦黏膜标本。分离信使核糖核酸(mRNA),并使用针对C3、补体因子P和SAA的引物和探针组,通过Taqman实时聚合酶链反应进行检测。对10种已知的TLRs进行标准聚合酶链反应。使用抗C3抗体对显微切片进行免疫组织化学检测。
对鼻窦样本mRNA的分析显示,CRS样本和对照标本中均表达所有10种TLRs。还检测到三种效应蛋白的表达,CRS患者中C3的mRNA水平通常高于SAA和备解素。正常对照中TLR或固有免疫蛋白表达未发现显著差异。鼻窦黏膜标本的免疫组织化学分析显示,C3染色范围为上皮组织的20%至85%。
这些研究表明,鼻窦黏膜表达参与固有免疫的基因,包括TLRs以及参与补体激活的蛋白质。我们推测,气道上皮在固有免疫受体受刺激时局部产生补体和急性期蛋白,可能在气道宿主防御以及CRS的发病机制中发挥重要作用。