Faure K, Leberre R, Guery B
Laboratoire de recherche en pathologie infectieuse, EA 2689, faculté de médecine de Lille, 59045 Lille, France.
Med Mal Infect. 2006 Feb;36(2):63-71. doi: 10.1016/j.medmal.2005.08.011. Epub 2006 Jan 5.
Surfactant-associated proteins A and D (SP-A and SP-D) are two pulmonary collectins that bind to bacterial, fungal and viral pathogens and have multiples classes of receptors on pneumocyte and macrophage membrane. They are chemoattractant for phagocytes, enhance uptake and killing of bacteria by macrophages and neutrophils. These molecules also act as activation ligand on macrophages and neutrophils to enhance phagocytosis, resulting in an increased bacterial clearance. Depending on activation of cells by stimuli, SP-A and SP-D modulate production of antimicrobial free radicals by phagocytes and secretion of cytokines. In vivo, SP-A deficient mice infected with Pseudomonas aeruginosa (P. aeruginosa) have decreased bacterial clearance and exacerbated inflammatory response in the lungs. Serious alterations in macrophages and increased production of reactive oxygen species were found in non-infected SP-D deficient mice. Patients with cystic fibrosis are frequently colonized by P. aeruginosa. Decreased levels of SP-A and SP-D have been measured in bronchoalveolar lavage fluid of these patients, as well as patients with acute pneumonia but no chronic lung disease. P. aeruginosa secretes various proteases, among them, elastase and protease IV have been found to degrade SP-A and SP-D and abrogate their immune function. However, further investigations are necessary to examine whether these deficiencies facilitate P. aeruginosa infections or stand as consequences.
表面活性物质相关蛋白A和D(SP-A和SP-D)是两种肺凝集素,它们可与细菌、真菌和病毒病原体结合,并在肺细胞和巨噬细胞膜上具有多种类型的受体。它们是吞噬细胞的趋化因子,可增强巨噬细胞和中性粒细胞对细菌的摄取和杀灭作用。这些分子还可作为巨噬细胞和中性粒细胞上的激活配体,增强吞噬作用,从而增加细菌清除率。根据刺激对细胞的激活情况,SP-A和SP-D可调节吞噬细胞产生抗菌自由基以及细胞因子的分泌。在体内,感染铜绿假单胞菌(P. aeruginosa)的SP-A缺陷小鼠的细菌清除率降低,肺部炎症反应加剧。在未感染的SP-D缺陷小鼠中发现巨噬细胞有严重改变,活性氧的产生增加。囊性纤维化患者经常被铜绿假单胞菌定植。在这些患者以及患有急性肺炎但无慢性肺病的患者的支气管肺泡灌洗液中,已检测到SP-A和SP-D水平降低。铜绿假单胞菌分泌多种蛋白酶,其中已发现弹性蛋白酶和蛋白酶IV可降解SP-A和SP-D并消除其免疫功能。然而,有必要进一步研究这些缺陷是促进了铜绿假单胞菌感染还是其后果。