Department of Pediatrics, Division of Clinical Immunology and Allergy, Institute of Basic Medical Sciences, College of Medicine, National Cheng-Kung University, Tainan, Taiwan.
Clin Exp Allergy. 2010 Jan;40(1):111-22. doi: 10.1111/j.1365-2222.2009.03367.x.
Surfactant protein D (SP-D), a secreted pattern recognition molecule associated with pulmonary innate immunity, has been shown to mediate the clearance of pathogens in multiple ways. However, how SP-D interacts with alveolar macrophages (AMs) and dendritic cells (DCs) during allergen exposure remains unclear.
This study was performed to characterize the immunomodulatory effects of SP-D on mite allergen (Dermatophagoides pteronyssinus, Der p)-induced inflammatory signalling in AMs and DCs.
Murine AM, alveolar macrophage cell line derived from BALB/c mice (MH-S cells), and human monocyte-derived dendritic cells (MDDC) were used as model systems. The production of nitric oxide (NO) and TNF-alpha, expression of surface Toll-like receptors (TLRs), and expression of the C-type lectin receptor known as dendritic cell (DC)-specific ICAM-grabbing non-integrin (DC-SIGN) were measured as a function of pretreatment with SP-D and subsequent exposure to Der p. Der p-dependent cellular activations that were modified by SP-D in these model systems were then identified.
Pretreatment of MH-S cells with SP-D reduced Der p-dependent production of NO, TNF-alpha, and the downstream activations of IL-1 receptor-associated kinase, mitogen activated protein kinase (MAPK) kinase, and nuclear factor-kappaB. SP-D interacted with CD14 such that CD14 binding to Der p was inhibited and Der p-induced signalling via TLRs was blocked. DC-SIGN expression was suppressed by Der p in MH-S and MDDC; this down-regulation of DC-SIGN expression was prevented by pretreatment with SP-D.
These results indicated that the inhibition of Der p-induced activation of MH-S and MDDC by SP-D is mediated through suppression of the CD14/TLR signalling pathway and maintenance of DC-SIGN expression, which may protect allergen-induced airway inflammation.
表面活性蛋白 D（SP-D）是一种与肺固有免疫相关的分泌型模式识别分子，已被证明可通过多种方式介导病原体的清除。然而，SP-D 在过敏原暴露期间如何与肺泡巨噬细胞（AMs）和树突状细胞（DCs）相互作用仍不清楚。
本研究旨在描述 SP-D 对 AMs 和 DCs 中螨过敏原（屋尘螨，Der p）诱导的炎症信号的免疫调节作用。
使用鼠 AM、源自 BALB/c 小鼠的肺泡巨噬细胞系（MH-S 细胞）和人单核细胞衍生的树突状细胞（MDDC）作为模型系统。作为预处理的功能，测量一氧化氮（NO）和 TNF-α的产生、表面 Toll 样受体（TLR）的表达以及称为树突状细胞（DC）特异性 ICAM 抓取非整合素（DC-SIGN）的 C 型凝集素受体的表达，随后暴露于 Der p。然后鉴定这些模型系统中 SP-D 修饰的 Der p 依赖性细胞激活。
SP-D 预处理 MH-S 细胞可减少 Der p 依赖性 NO、TNF-α的产生，以及白细胞介素 1 受体相关激酶、丝裂原激活蛋白激酶（MAPK）激酶和核因子-κB 的下游激活。SP-D 与 CD14 相互作用，使 CD14 与 Der p 的结合受到抑制，TLR 介导的 Der p 信号受到阻断。Der p 在 MH-S 和 MDDC 中抑制 DC-SIGN 的表达；SP-D 的预处理可防止这种 DC-SIGN 表达的下调。
这些结果表明，SP-D 通过抑制 CD14/TLR 信号通路和维持 DC-SIGN 表达来抑制 Der p 诱导的 MH-S 和 MDDC 的激活，这可能保护过敏原诱导的气道炎症。
