In vivo rescue of alveolar macrophages from SP-A knockout mice with exogenous SP-A nearly restores a wild type intracellular proteome; actin involvement.
In vivo rescue of alveolar macrophages from SP-A knockout mice with exogenous SP-A nearly restores a wild type intracellular proteome; actin involvement.
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DOI：
10.1186/1477-5956-9-67
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发表时间：
2011-10-28
期刊：
影响因子：
2
通讯作者：
Floros J
中科院分区：
文献类型：
--
作者：
Phelps DS;Umstead TM;Quintero OA;Yengo CM;Floros J
缺乏表面活性剂蛋白a （SP-A-/-；敲除；KO）的小鼠对感染和损伤的易感性增加。尽管KO与野生型（WT）之间的许多支气管肺泡灌洗（BAL）蛋白差异在感染后KO中迅速逆转，但其临床过程仍然受到损害。我们研究了SP-A在基础条件下对肺泡巨噬细胞（AM）蛋白质组的影响。雄性SP-A KO小鼠接受SP-A处理（5微克/只），在6或18小时内处死。用2D-DIGE联合MALDI-ToF/ToF检测KO、sp - a处理的KO和WT小鼠的AM蛋白组，用phalloidon染色检测AM肌动蛋白分布。我们观察到：a) 76个鉴定的蛋白质中有45个在WT或外源性sp - a处理下与KO有显著差异（增加和减少）。其中包括肌动蛋白相关蛋白/细胞骨架蛋白（参与运动、吞噬、内吞作用）、细胞内信号传导蛋白、细胞分化/调节蛋白、炎症调节蛋白、蛋白酶/伴侣蛋白功能蛋白，以及nrf2介导的氧化应激反应途径相关蛋白；b) sp - a诱导的改变使KO的AM蛋白质组与WT相似；c) SP-A处理改变了细胞大小和f -肌动蛋白分布。这些差异可能会增强AM功能。观察结果首次表明，在基础或非刺激条件下，急性体内SP-A治疗KO小鼠，会影响多种AM蛋白的表达，改变f -肌动蛋白的分布，并可以恢复大部分WT表型。我们假设sp - a介导的AM表达谱使其处于“准备”状态，以成功地执行其先天免疫功能并确保肺部健康。
Mice lacking surfactant protein-A (SP-A-/-; knockout; KO) exhibit increased vulnerability to infection and injury. Although many bronchoalveolar lavage (BAL) protein differences between KO and wild-type (WT) are rapidly reversed in KO after infection, their clinical course is still compromised. We studied the impact of SP-A on the alveolar macrophage (AM) proteome under basal conditions. Male SP-A KO mice were SP-A-treated (5 micrograms/mouse) and sacrificed in 6 or 18 hr. The AM proteomes of KO, SP-A-treated KO, and WT mice were studied by 2D-DIGE coupled with MALDI-ToF/ToF and AM actin distribution was examined by phalloidon staining. We observed: a) significant differences from KO in WT or exogenous SP-A-treated in 45 of 76 identified proteins (both increases and decreases). These included actin-related/cytoskeletal proteins (involved in motility, phagocytosis, endocytosis), proteins of intracellular signaling, cell differentiation/regulation, regulation of inflammation, protease/chaperone function, and proteins related to Nrf2-mediated oxidative stress response pathway; b) SP-A-induced changes causing the AM proteome of the KO to resemble that of WT; and c) that SP-A treatment altered cell size and F-actin distribution. These differences are likely to enhance AM function. The observations show for the first time that acute in vivo SP-A treatment of KO mice, under basal or unstimulated conditions, affects the expression of multiple AM proteins, alters F-actin distribution, and can restore much of the WT phenotype. We postulate that the SP-A-mediated expression profile of the AM places it in a state of "readiness" to successfully conduct its innate immune functions and ensure lung health.
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DOI：
10.1054/plef.2001.0309
发表时间：
2001-10-01
影响因子：
3
作者：
Blanco, O;Catalá, A
通讯作者：
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DOI：
10.1152/ajplung.00082.2003
发表时间：
2003-10-01
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Schlesinger, LS
影响因子：
3.6
作者：
Famuyide ME;Hasday JD;Carter HC;Chesko KL;He JR;Viscardi RM
通讯作者：
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DOI：
10.1016/j.bbapap.2006.06.017
发表时间：
2006-11-01
影响因子：
3.2
作者：
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