Haagsman Henk P, Hogenkamp Astrid, van Eijk Martin, Veldhuizen Edwin J A
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Neonatology. 2008;93(4):288-94. doi: 10.1159/000121454. Epub 2008 Jun 5.
Respiratory pathogens encounter various lines of defenses before infection of the host is established. The innate immune response represents an important first-line protection mechanism against potentially pathogenic microorganisms during early stages of infection of the naive host. Important players in this host defense system are 'collectins', a class of soluble innate immune proteins. Well-characterized members of the collectin family are the surfactant proteins A (SP-A) and D (SP-D). These collectins are expressed in the lung and also in extrapulmonary mucosal tissues. Collectins are secreted as multimers resulting in trimeric clustering of the lectin domains which enables recognition of evolutionary conserved sugar patterns present on the surface of a large variety of pathogens. Binding to collectins may lead to direct agglutination and neutralization of pathogens, to opsonization in order to present bound microbes directly to phagocytes, to modulation of the inflammatory response and to regulation of dendritic cell and T cell functions. In pulmonary tissue, this early acute-phase-like response can be regarded as a crucial layer of protection against a vast array of pathogens that escape the physical barriers and threaten to infect the delicate respiratory epithelium. An important clinical application may be the inhalation, or instillation of collectin-based drugs as part of surfactant therapy, to prevent and treat infectious and inflammatory diseases of newborn infants.
在宿主被感染之前,呼吸道病原体要面对多种防御机制。固有免疫反应是初免宿主感染早期针对潜在致病微生物的重要一线保护机制。该宿主防御系统中的重要成员是“凝集素”,这是一类可溶性固有免疫蛋白。凝集素家族中特性明确的成员是表面活性蛋白A(SP-A)和D(SP-D)。这些凝集素在肺组织以及肺外黏膜组织中均有表达。凝集素以多聚体形式分泌,导致其凝集素结构域三聚体化,从而能够识别多种病原体表面存在的进化保守糖基模式。与凝集素结合可能导致病原体直接凝集和中和、调理作用以便将结合的微生物直接呈递给吞噬细胞、调节炎症反应以及调节树突状细胞和T细胞功能。在肺组织中,这种早期类似急性期的反应可被视为针对大量突破物理屏障并可能感染脆弱呼吸道上皮的病原体的关键保护层。一个重要的临床应用可能是吸入或滴注基于凝集素的药物作为表面活性剂疗法的一部分,以预防和治疗新生儿的感染性和炎性疾病。