Wang J Y, Shieh C C, You P F, Lei H Y, Reid K B
Departments of Pediatrics, and Microbiology and Immunology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan.
Am J Respir Crit Care Med. 1998 Aug;158(2):510-8. doi: 10.1164/ajrccm.158.2.9709111.
The role of pulmonary surfactant proteins in the pathogenesis of airway inflammation and the impact on asthma has not been elucidated. This study was designed to examine the effect of surfactant proteins A (SP-A) and D (SP-D) on phytohemagglutinin- (PHA) and mite allergen Dermatophagoides pteronyssinus (Der p)-induced histamine release and the proliferation of peripheral blood mononuclear cells (PBMC) in children with asthma in stable condition (n = 21), asthmatic children during acute attacks (n = 9), and age-matched control subjects (n = 7). The results show that SP-A and SP-D were able to reduce the incorporation of [3H]thymidine into PBMC in a dose-dependent manner. In addition to the intact, native SP-A and SP-D proteins, a recombinant peptide composed of the neck and carbohydrate recognition domain (CRD) of SP-D [SP-D(N/CRD)] was also found to have the same suppressive effect on lymphocyte proliferation. This effect was abolished by the presence of 100 mM mannose (for SP-A) or maltose (for SP-D) in the culture medium, which suggested that the CRD regions of SP-A and SP-D may interact with the carbohydrate structures on the surface molecules of lymphocytes. The inhibitory effects of surfactant proteins on PHA- and Der p-stimulated lymphocyte responses were observed in stable asthmatic children and age-matched control subjects, while only a mild suppression (< 25%) was seen in activated lymphocytes derived from asthmatic children with acute attacks. SP-A and SP-D were also found to inhibit allergen-induced histamine release, in a dose-dependent manner, in the diluted whole blood of asthmatic children. We conclude that both SP-A and SP-D can inhibit histamine release in the early phase of allergen provocation and suppress lymphocyte proliferation in the late phase of bronchial inflammation, the two essential steps in the development of asthmatic symptoms. It appears that SP-A and SP-D may be protective against the pathogenesis of asthma.
肺表面活性物质蛋白在气道炎症发病机制中的作用以及对哮喘的影响尚未阐明。本研究旨在检测表面活性物质蛋白A（SP-A）和D（SP-D）对处于稳定期的哮喘儿童（n = 21）、急性发作期的哮喘儿童（n = 9）以及年龄匹配的对照受试者（n = 7）的外周血单个核细胞（PBMC）在植物血凝素（PHA）和螨过敏原屋尘螨（Der p）诱导下组胺释放及增殖的影响。结果显示，SP-A和SP-D能够以剂量依赖的方式减少[3H]胸腺嘧啶核苷掺入PBMC。除了完整的天然SP-A和SP-D蛋白外，由SP-D的颈部和碳水化合物识别结构域（CRD）组成的重组肽[SP-D（N/CRD）]也被发现对淋巴细胞增殖具有相同的抑制作用。培养基中存在100 mM甘露糖（针对SP-A）或麦芽糖（针对SP-D）可消除这种作用，这表明SP-A和SP-D的CRD区域可能与淋巴细胞表面分子上的碳水化合物结构相互作用。在稳定期哮喘儿童和年龄匹配的对照受试者中观察到表面活性物质蛋白对PHA和Der p刺激的淋巴细胞反应具有抑制作用，而在急性发作期哮喘儿童来源的活化淋巴细胞中仅观察到轻度抑制（< 25%）。还发现SP-A和SP-D能够以剂量依赖的方式抑制哮喘儿童稀释全血中过敏原诱导的组胺释放。我们得出结论，SP-A和SP-D均可在过敏原激发的早期阶段抑制组胺释放，并在支气管炎症的后期阶段抑制淋巴细胞增殖，这是哮喘症状发展的两个关键步骤。看来SP-A和SP-D可能对哮喘发病机制具有保护作用。
