肺表面活性物质相关蛋白A、D的研究进展

肺表面活性物质是由肺泡Ⅱ型上皮细胞和气道Clara细胞合成并分泌的脂蛋白复合物,是构成呼吸系统防御功能的一部分.其中90%是磷脂,10%是蛋白质.蛋白质又分为疏水性蛋白和亲水性蛋白,前者包括肺表面活性物质相关蛋白B、C(SP-B、SP-C);后者包括肺表面活性物质相关蛋白A、D(SP-A、SP-D)[1],其中SP-A、SP-D在宿主防御感染和炎症方面发挥重要作用.现将SP-A、D的研究进展综述如下.     

肺表面活性物质相关蛋白A与D在肺结核诊断中的研究

目的 研究肺表面活性物质相关蛋白A、D（pulmonary surfactant associated protein A、D,SP-A、SP-D）在肺结核患者中的表达，探讨2者的相关性。 方法 采用ELISA方法检测涂阳肺结核50例，涂阴肺结核51例，慢性阻塞性肺疾病（COPD）患者30例及健康人85名血清及痰液中SP-A、SP-D的表达情况。 结果 涂阳肺结核组痰液中SP-A、SP-D的表达与痰液中结核分枝杆菌的含菌量有相关性；血清SP-A、SP-D在肺结核组高表达（P<0.05），痰SP-D在肺结核组低表达（P<0.01）。 结论 SP-A、SP-D的表达与肺结核之间可能有相关性，或可成为协助肺结核诊断的辅助指标。     

巨噬细胞与结核分枝杆菌的免疫反应的研究进展

巨噬细胞是结核分枝杆菌在机体内的主要宿主细胞.细胞介导的免疫反应是机体抗结核分枝杆菌的主要免疫保护机制,巨噬细胞可通过吞噬、溶酶体融合,提呈结核分枝杆菌抗原,产生多种细胞因子、反应氧中间产物和反应氮中间产物,以及细胞凋亡等多种途径来杀灭结核分枝杆菌;同时,结核分枝杆菌也可采取各种方式来逃逸巨噬细胞的免疫作用.本文就巨噬细胞与结核分枝杆菌的免疫反应的研究进展作一综述.     

巨噬细胞与结核分枝杆菌的免疫反应的研究进展

巨噬细胞是结核分枝杆菌在机体内的主要宿主细胞.细胞介导的免疫反应是机体抗结核分枝杆菌的主要免疫保护机制,巨噬细胞可通过吞噬、溶酶体融合,提呈结核分枝杆菌抗原,产生多种细胞因子、反应氧中间产物和反应氮中间产物,以及细胞凋亡等多种途径来杀灭结核分枝杆菌;同时,结核分枝杆菌也可采取各种方式来逃逸巨噬细胞的免疫作用.本文就巨噬细胞与结核分枝杆菌的免疫反应的研究进展作一综述.     

巨噬细胞与结核分枝杆菌的免疫反应的研究进展

巨噬细胞是结核分枝杆菌在机体内的主要宿主细胞.细胞介导的免疫反应是机体抗结核分枝杆菌的主要免疫保护机制,巨噬细胞可通过吞噬、溶酶体融合,提呈结核分枝杆菌抗原,产生多种细胞因子、反应氧中间产物和反应氮中间产物,以及细胞凋亡等多种途径来杀灭结核分枝杆菌;同时,结核分枝杆菌也可采取各种方式来逃逸巨噬细胞的免疫作用.本文就巨噬细胞与结核分枝杆菌的免疫反应的研究进展作一综述.     

肺结核患者血清肺表面活性物质相关蛋白质-A水平检测的意义

肺表面活性物质相关蛋白质(pulmonary surfactant associated protein,SP)-A是肺表面活性物质中含量最丰富的蛋白质成分,主要分布于支气管表面和肺泡气液界面,属于C型胶凝素家族的重要成员[1].已有的研究结果证实,肺表面活性物质在肺部感染及局部炎症反应的免疫调节中具有重要意义,原发介导免疫调节功能的物质是SP-A及SP-D [2-3],SP-A水平与肺结核的易感性有关[4-5].本研究旨在探讨SP-A在肺结核患者血清中的表达情况.     

粒-巨噬细胞集落刺激因子及肺表面活性蛋白在肺泡蛋白沉积症患者肺内的表达

目的通过观察成人特发性肺泡蛋白沉积症(PAP)患者肺部粒-巨噬细胞集落刺激因子(GM-CSF)及其受体蛋白以及肺泡表面活性蛋白的表达,探讨PAP的发病机制。方法用SP免疫组化技术检测6例PAP患者(PAP组)及6例对照者(对照组)肺组织肺泡巨噬细胞及Ⅱ型肺泡上皮细胞GM-CSF、GM-CSF/IL-3/IL-5共同β链受体(GM-CSFβcR)、肺表面活性蛋白(SP)-A和SP-D蛋白表达。结果(1)肺泡巨噬细胞2组表达GM-CSF蛋白均较弱,阳性细胞数少,组间比较差异无统计学意义(P=0.818);2组均表达GM-CSFβcR蛋白,对照组显著高于PAP组(P=0.002);2组均表达SP-A蛋白,且PAP组呈阳性反应,但阳性细胞数少,积分指数显著低于对照组(P=0.004);2组表达SP-D蛋白差异无统计学意义(P=0.24)。(2)Ⅱ型肺泡上皮细胞2组均表达SP-A和SP-D蛋白,组间比较差异无统计学意义(P=0.818,P=0.485);对照组少数表达GM-CSFβcR蛋白,PAP组无GM-CSFβcR蛋白表达;2组均无GM-CSF蛋白表达。结论肺泡巨噬细胞表达GM-CSFβcR蛋白减少可能与成人特发性PAP肺泡巨噬细胞功能障碍有关。     

肺泡表面相关蛋白A和D研究进展与意义

肺泡表面相关蛋白A(pulmonary surfactant-associated protein A,SP-A)、SP-D属于凝集索家族,与肺的天然免疫有着很大的相关性,能够与多种微生物表面的糖类分子以及细胞内核酸分子相结合,介导免疫功能,促使细菌、病毒、真菌以及凋亡和坏死细胞的清除和局限,同时能够与免疫细胞表面分子或者受体结合,调节树突状细胞、巨噬细胞等免疫细胞的功能.许多研究学者关于SP-A和SP-D在肺泡灌洗液、血液及其他体液中的水平有着深刻的研究,证明了SP-A和SP-D与肺内多种炎症、感染性疾病有关.除此之外,有研究学者发现相关重组蛋白在SP-A和SP-D缺陷的肺部感染性疾病的小鼠中具有一定的治疗作用.本文总结了SP-A和SP-D目前研究的深度以及和多种疾病的关系.     

肺泡表面相关蛋白A和D研究进展与意义

肺泡表面相关蛋白A(pulmonary surfactant-associated protein A,SP-A)、SP-D属于凝集索家族,与肺的天然免疫有着很大的相关性,能够与多种微生物表面的糖类分子以及细胞内核酸分子相结合,介导免疫功能,促使细菌、病毒、真菌以及凋亡和坏死细胞的清除和局限,同时能够与免疫细胞表面分子或者受体结合,调节树突状细胞、巨噬细胞等免疫细胞的功能.许多研究学者关于SP-A和SP-D在肺泡灌洗液、血液及其他体液中的水平有着深刻的研究,证明了SP-A和SP-D与肺内多种炎症、感染性疾病有关.除此之外,有研究学者发现相关重组蛋白在SP-A和SP-D缺陷的肺部感染性疾病的小鼠中具有一定的治疗作用.本文总结了SP-A和SP-D目前研究的深度以及和多种疾病的关系.     

肺泡表面相关蛋白A和D研究进展与意义

肺泡表面相关蛋白A(pulmonary surfactant-associated protein A,SP-A)、SP-D属于凝集索家族,与肺的天然免疫有着很大的相关性,能够与多种微生物表面的糖类分子以及细胞内核酸分子相结合,介导免疫功能,促使细菌、病毒、真菌以及凋亡和坏死细胞的清除和局限,同时能够与免疫细胞表面分子或者受体结合,调节树突状细胞、巨噬细胞等免疫细胞的功能.许多研究学者关于SP-A和SP-D在肺泡灌洗液、血液及其他体液中的水平有着深刻的研究,证明了SP-A和SP-D与肺内多种炎症、感染性疾病有关.除此之外,有研究学者发现相关重组蛋白在SP-A和SP-D缺陷的肺部感染性疾病的小鼠中具有一定的治疗作用.本文总结了SP-A和SP-D目前研究的深度以及和多种疾病的关系.     

Regulation of inflammation and bacterial clearance by lung collectins

Abstract:   Pulmonary surfactant proteins (SP) A and D play important roles in the innate immune system of the lung. These proteins belong to the collectin subgroup in which lectin domains are associated with collagenous structures. To obtain a better understanding of how lung collectins modulate cellular responses, the authors investigated whether SP-A interacts with the toll-like receptor 2 (TLR2). SP-A bound to TLR2 and inhibited interactions between TLR2 and TLR2-ligands such as peptidoglycan (PGN) and zymosan. NF-κB activation and tumour necrosis factor-α expression induced by PGN or zymosan were significantly inhibited in the presence of SP-A. Lung collectins may act as inhibitors of lung inflammation in respiratory infections. The authors also examined the effects of lung collectins on the phagocytosis of bacteria by alveolar macrophages. Lung collectins enhanced the uptake of S. pneumoniae or M. avium by alveolar macrophages. It was demonstrated that the direct interaction of lung collectins with macrophages resulted in increased cell surface expression of scavenger receptor A or mannose receptor, which are responsible for phagocytosis. This study has emphasized the biological relevance of SP-A and SP-D against various respiratory infections, however, a more complete understanding of the molecular mechanism is required.     

Efficient and rapid isolation and purification of mouse alveolar type II epithelial cells

ABSTRACT The alveolar surface is covered by an epithelium composed of 2 main cell types: type I and type II cells. Alveolar type II (ATII) cells have a distinct morphology with apical microvilli and characteristic lamellar bodies, which are the intracellular storage form of pulmonary surfactant. ATII cells play an important role in innate immunity and produce and secrete pulmonary surfactant. They proliferate to restore the epithelium after damage to the more sensitive type I cells. We developed an efficient and rapid method to isolate and purify ATII cells from mice. Alveolar epithelial cells were dissociated in the murine lung with dispase and lung tissue was gently minced with a GentleMACS Dissociator. ATII cell purification was performed using negative depletion with CD45 MicroBeads and positive selection for the epithelial-cell adhesion molecule (Ep-CAM) by magnetic labeling with Streptavidin MicroBeads in MACS LS columns. The purity of these cells as measured by flow cytometry was up to 92.1% and 91.1% for co-staining with Ep-CAM and cytokeratin and co-staining with Ep-CAM and SP-A, respectively. The resulting ATII cell population has a high purity, viability, and yield. The phenotype of isolated and cultured ATII cells was confirmed by electron micrographs, expression of surfactant proteins (SP-A, proSP-B, mature SP-B, proSP-C, SP-D), and lysophosphatidylcholine acyltransferase (LPCAT) by western blotting and immunocytofluorescence. This protocol is based on surface antigens and our data demonstrated that murine ATII cells can be rapidly isolated, efficiently purified, and effectively cultured.     

KL-6, surfactant protein A and D in bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis.

BACKGROUND: KL-6, and surfactant protein A (SP-A) and surfactant protein D (SP-D) derived from alveolar type II cells and/or bronchiolar epithelial cells have been reported to be useful markers for interstitial lung diseases. OBJECTIVE: The aim of this study was to measure the levels of these molecules in bronchoalveolar lavage fluid (BALF) from patients with pulmonary sarcoidosis to investigate their relationship with other markers of inflammatory activity. METHODS: We measured KL-6, SP-A and SP-D levels in BALF from patients with pulmonary sarcoidosis using an ELISA. RESULTS: KL-6 and SP-D, but not SP-A levels were significantly increased in pulmonary sarcoidosis compared with controls. KL-6, SP-A and SP-D levels were significantly correlated with each other. KL-6 and SP-D levels were relatively and significantly correlated with the percentage of lymphocytes in BALF. KL-6, SP-D, but not SP-A levels were significantly correlated with the concentration of albumin in BALF. There was no significant correlation between KL-6, SP-A, or SP-D levels and chest X-ray findings, angiotensin-converting enzyme levels, or CD4/CD8 ratio in BALF. CONCLUSIONS: We conclude that KL-6 and SP-D levels in BALF were increased in pulmonary sarcoidosis. Since these markers are specifically derived from epithelial cells, it is considered that KL-6 and SP-D levels are reflecting damage or release of these markers from epithelial cells due to the inflammatory response.     

Immunomodulatory roles of surfactant proteins A and D: implications in lung disease

Surfactant, a lipoprotein complex, was originally described for its essential role in reducing surface tension at the air-liquid interface of the lung; however, it is now recognized as being a critical component in lung immune host defense. Surfactant proteins (SP)-A and -D are pattern recognition molecules of the collectin family of C-type lectins. SP-A and SP-D are part of the innate immune system and regulate the functions of other innate immune cells, such as macrophages. They also modulate the adaptive immune response by interacting with antigen-presenting cells and T cells, thereby linking innate and adaptive immunity. Emerging studies suggest that SP-A and SP-D function to modulate the immunologic environment of the lung so as to protect the host and, at the same time, modulate an overzealous inflammatory response that could potentially damage the lung and impair gas exchange. Numerous polymorphisms of SPs have been identified that may potentially possess differential functional abilities and may act via different receptors to ultimately alter the susceptibility to or severity of lung diseases.     

Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D

Surfactant protein D (SP-D) is one of two collectins found in the pulmonary alveolus. On the basis of homology with other collectins, potential functions for SP-D include roles in innate immunity and surfactant metabolism. The SP-D gene was disrupted in embryonic stem cells by homologous recombination to generate mice deficient in SP-D. Mice heterozygous for the mutant SP-D allele had SP-D concentrations that were approximately 50% wild type but no other obvious phenotypic abnormality. Mice totally deficient in SP-D were healthy to 7 months but had a progressive accumulation of surfactant lipids, SP-A, and SP-B in the alveolar space. By 8 weeks the alveolar phospholipid pool was 8-fold higher than wild-type littermates. There was also a 10-fold accumulation of alveolar macrophages in the null mice, and many macrophages were both multinucleated and foamy in appearance. Type II cells in the null mice were hyperplastic and contained giant lamellar bodies. These alterations in surfactant homeostasis were not associated with detectable changes in surfactant surface activity, postnatal respiratory function, or survival. The findings in the SP-D-deficient mice suggest a role for SP-D in surfactant homeostasis.     

结核分枝杆菌肝素结合血凝黏附素与结核病

结核分枝杆菌肝素结合血凝黏附素是一种表面蛋白,有3个功能结构域,其C末端在翻译后进行甲基化修饰,与其免疫特性相关.可结合硫酸化糖,可通过补体C3介导与巨噬细胞的结合,与上皮细胞结合在肺外结核发病中有重要作用.通过对其细胞免疫及体液免疫作用的研究发现,其在诊断中有较好的作用,在免疫预防及免疫治疗中有广阔的应用前景.