Haczku Angela
Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
J Allergy Clin Immunol. 2008 Nov;122(5):861-79; quiz 880-1. doi: 10.1016/j.jaci.2008.10.014.
The acute inflammatory airway response is characterized by a time-dependent onset followed by active resolution. Emerging evidence suggests that epithelial cells of the proximal and distal air spaces release host defense mediators that can facilitate both the initiation and the resolution part of inflammatory airway changes. These molecules, also known as the hydrophilic surfactant proteins (surfactant protein [SP]-A and SP-D) belong to the class of collagenous lectins (collectins). The collectins are a small family of soluble pattern recognition receptors containing collagenous regions and C-type lectin domains. SP-A and SP-D are most abundant in the lung. Because of their structural uniqueness, specific localization, and functional versatility, lung collectins are important players of the pulmonary immune responses. Recent studies in our laboratory and others indicated significant associations of lung collectin levels with acute and chronic airway inflammation in both animal models and patients, suggesting the usefulness of these molecules as disease biomarkers. Research on wild-type and mutant recombinant molecules in vivo and in vitro showed that SP-A and SP-D bind carbohydrates, lipids, and nucleic acids with a broad-spectrum specificity and initiate phagocytosis of inhaled pathogens as well as apoptotic cells. Investigations on gene-deficient and conditional overexpresser mice indicated that lung collectins also directly modulate innate immune cell function and T-cell-dependent inflammatory events. Thus, these molecules have a unique, dual-function capacity to induce pathogen elimination and control proinflammatory mechanisms, suggesting a potential suitability for therapeutic prevention and treatment of chronic airway inflammation. This article reviews evidence supporting that the lung collectins play an immune-protective role and are essential for maintenance of the immunologic homeostasis in the lung.
急性炎症性气道反应的特征是具有时间依赖性的发作，随后是主动消退。新出现的证据表明，近端和远端气腔的上皮细胞释放宿主防御介质，这些介质可促进炎症性气道变化的起始和消退阶段。这些分子，也称为亲水性表面活性蛋白（表面活性蛋白[SP]-A和SP-D），属于胶原凝集素（collectins）类。凝集素是一个小的可溶性模式识别受体家族，包含胶原区域和C型凝集素结构域。SP-A和SP-D在肺中含量最为丰富。由于其结构独特、定位特异且功能多样，肺凝集素是肺部免疫反应的重要参与者。我们实验室和其他机构最近的研究表明，在动物模型和患者中，肺凝集素水平与急性和慢性气道炎症存在显著关联，这表明这些分子作为疾病生物标志物的有用性。对野生型和突变重组分子的体内和体外研究表明，SP-A和SP-D以广谱特异性结合碳水化合物、脂质和核酸，并启动对吸入病原体以及凋亡细胞的吞噬作用。对基因缺陷和条件性过表达小鼠的研究表明，肺凝集素还直接调节先天免疫细胞功能和T细胞依赖性炎症事件。因此，这些分子具有诱导病原体清除和控制促炎机制的独特双重功能，提示其在慢性气道炎症的治疗性预防和治疗中具有潜在适用性。本文综述了支持肺凝集素发挥免疫保护作用且对维持肺部免疫稳态至关重要的证据。
