Fujita Masaki, Shannon John M, Ouchi Hiroshi, Voelker Dennis R, Nakanishi Yoichi, Mason Robert J
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka, Japan.
Cytokine. 2005 Jul 7;31(1):25-33. doi: 10.1016/j.cyto.2005.02.006.
Surfactant protein A (SP-A) and surfactant protein D (SP-D) are important components of innate immunity that can modify the inflammatory response. However, alterations and regulation of SP-A and SP-D in acute and chronic inflammation are not well defined. In addition, serum SP-D may serve as a biomarker of lung inflammation. We determined the expression of SP-A and SP-D in murine models. To study acute inflammation, we instilled bleomycin intrabronchially. To study chronic lung inflammation, we used a transgenic mouse that overexpresses tumor necrosis factor (TNF)-alpha under the control of the SP-C promoter. These mice have a chronic mononuclear cell infiltration, airspace enlargement, pulmonary hypertension, and focal pulmonary fibrosis. In acute inflammation model, levels of mRNA for all surfactant proteins were reduced after bleomycin administration. However, serum SP-D was increased from days 7 to 28 after instillation. In chronic inflammation model, SP-D mRNA expression was increased, whereas the expression of SP-A, SP-B and SP-C was reduced. Both serum and lung SP-D concentrations were increased in chronic lung inflammation. These data clarified profile of SP-A and SP-D in acute and chronic inflammation and indicated that serum SP-D can serve as a biomarker of lung inflammation in both acute and chronic lung injury in mice.
表面活性蛋白A(SP-A)和表面活性蛋白D(SP-D)是先天性免疫的重要组成部分,可调节炎症反应。然而,SP-A和SP-D在急性和慢性炎症中的变化及调控尚不明确。此外,血清SP-D可能是肺部炎症的生物标志物。我们在小鼠模型中测定了SP-A和SP-D的表达。为研究急性炎症,我们经支气管内注入博来霉素。为研究慢性肺部炎症,我们使用了一种在SP-C启动子控制下过度表达肿瘤坏死因子(TNF)-α的转基因小鼠。这些小鼠存在慢性单核细胞浸润、气腔扩大、肺动脉高压和局灶性肺纤维化。在急性炎症模型中,博来霉素给药后所有表面活性蛋白的mRNA水平均降低。然而,滴注后第7天至28天血清SP-D升高。在慢性炎症模型中,SP-D mRNA表达增加,而SP-A、SP-B和SP-C的表达降低。慢性肺部炎症时血清和肺组织中的SP-D浓度均升高。这些数据阐明了SP-A和SP-D在急性和慢性炎症中的情况,并表明血清SP-D可作为小鼠急性和慢性肺损伤中肺部炎症的生物标志物。