Surfactant protein-A enhances uptake of respiratory syncytial virus by monocytes and U937 macrophages
Surfactant protein-A enhances uptake of respiratory syncytial virus by monocytes and U937 macrophages
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DOI：
10.1165/ajrcmb.23.5.3771
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发表时间：
2000-11-01
影响因子：
6.4
通讯作者：
Shepherd, VL
中科院分区：
文献类型：
--
作者：
Barr, FE;Pedigo, H;Shepherd, VL
表面活性蛋白(SP)-A是一种已知的对多种肺部病原体的调理蛋白。SP-A通过与吞噬细胞(如外周血单核细胞和肺泡巨噬细胞)上发现的SP-A受体(SP-AR)相互作用，促进这些病原体的摄取。呼吸道合胞病毒(RSV)是儿童最重要的呼吸道病原体。最近的研究表明，在呼吸道合胞病毒毛细支气管炎和肺炎中，SP-A水平可能降低。在本研究中，我们研究了SP-A在PBMC和U937巨噬细胞摄取RSV中的作用。U937巨噬细胞是已知表达SP-AR的人巨噬细胞系。此外，我们还研究了SP-A介导的RSV摄取对这些细胞产生肿瘤坏死因子(TNF)-α和白介素10(IL-10)的影响，因为对反复RSV感染的不完全免疫部分归因于巨噬细胞的异常细胞因子反应，SP-A以剂量依赖的方式促进PBMC对荧光标记的RSV(RSV-FITC)的结合和摄取以单核细胞的荧光百分率和单个细胞的线性平均荧光(IMF)为指标，以10~15µg/mlSP-A作用最强。SP-A还可促进U937巨噬细胞摄取RSV-FITC，其中以20µg/mlSP-A的作用最强。在加入RSV后12小时，单纯RSV对PBMC产生的TNF-α有轻微的促进作用，而对U937巨噬细胞产生的TNF-α则有轻微的抑制作用。SP-A介导的RSV摄取显著增加了PBMC产生的TNF-α，并逆转了RSV对U937巨噬细胞产生的抑制作用。RSV显著促进两种细胞产生IL-10，这种作用被SP-A介导的摄取逆转。这些发现表明，SP-A是RSV的一个重要调控素，SP-A介导的RSV摄取可能会改变一些不寻常的细胞因子反应，这些细胞因子反应被认为参与了对反复感染的不完全免疫。
Surfactant protein (SP)-A is a known opsonin for a variety of pulmonary pathogens. SP-A enhances ingestion of these pathogens by interaction with an SP-A receptor (SP-AR) found on phagocytic cells such as peripheral blood monocytes (PBMC) and alveolar macrophages. Respiratory syncytial virus (RSV) is the most important respiratory pathogen in children. Recent studies have indicated that SP-A levels may be decreased in RSV bronchiolitis and pneumonia, In this study we examined the role of SP-A in uptake of RSV by both PBMC and U937 macrophages, a human macrophage cell line known to express SP-ARs, In addition, we studied the effect of SP-A-mediated uptake of RSV on production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 by these cells because incomplete immunity to recurrent RSV infection has been partially attributed to abnormal cytokine responses by macrophages, SP-A enhanced binding and uptake of fluorescently labeled RSV (RSV-FITC) by PBMC in a dose-dependent manner, with a maximal effect seen with 10 to 15 mug/ml SP-A as measured by both percent fluorescent monocytes and linear mean fluorescence (Imf) of individual cells. SP-A also enhanced uptake of RSV-FITC by U937 macrophages, with a maximal effect seen with 20 mug/ml SP-A as measured by both percent fluorescent monocytes and Imf, With respect to TNF-alpha levels, RSV alone slightly enhanced TNF-alpha production by PBMC and decreased TNF-alpha production by U937 macrophages measured at 12 h after addition of RSV. SP-A-mediated uptake of RSV significantly enhanced TNF-alpha production by PBMC and reversed the RSV-induced depression of TNF-alpha by U937 macrophages. RSV significantly enhanced IL-10 production by both cell types, which was reversed by SP-A-mediated uptake. These findings suggest that SP-A is an important opsonin for RSV and that SP-A-mediated uptake of RSV may alter some of the unusual cytokine responses that are postulated to be involved in incomplete immunity to recurrent infection.