Acyl Homoserine Lactones Induce Early Response in the Airway
Acyl Homoserine Lactones Induce Early Response in the Airway
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DOI：
10.1002/ar.20866
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发表时间：
2009-03-01
影响因子：
2
通讯作者：
Osculati, Francesco
中科院分区：
文献类型：
--
作者：
Sbarbati, Andrea;Tizzano, Marco;Osculati, Francesco
酰基高丝氨酸内酯（AHL）是革兰氏阴性菌群体感应中的细胞间信号分子。我们研究了体内气管内施用AHLs（即，铜绿假单胞菌和B. cepacia）来检验AHLs也作用于气道细胞，改变在粘膜防御中重要的分泌机制的假设。处理后1小时，N-丁酰-高丝氨酸内酯（C4-HL）引起细胞外间隙扩张，纤毛丢失，分泌物质减少，上皮细胞中存在坏死前元素，而N-辛酰-高丝氨酸内酯（C8-HL）引起上皮细胞轻度病变。用C4-或C8-HL处理后，使用CC 10抗体发现免疫反应性降低。在超微结构检查中，扩张的线粒体是明显的纤毛和分泌细胞，而孤立的化学感觉细胞出现更好地保存，显示方面的核质激活。使用微阵列分析，我们发现下调早期基因Fos和Egr 1在所有AHL治疗标本。C4-或C8-HL给药后的体内药理学磁共振成像显示，给药后5分钟首次评价时气管分泌物轻微增加，随后几分钟内无增加。总之，AHL诱导早期粘膜反应，纤毛细胞和分泌细胞腺瘤是阿勒作用的主要细胞学靶点。我们的研究结果表明，阿勒的作用不仅限于激活同种细菌，而且还改变了先天性气道防御机制。Anat Rec，292：439-448，2009. (C)2009 WileyLiss，Inc.
Acyl homoserine lactones (AHLs) are intercellular signaling molecules used in quorum sensing by Gram-negative bacteria. We studied the early effects on the rat airway of in vivo intratracheal administration of AHLs (i.e., P. aeruginosa and B. cepacia) to test the hypothesis that AHLs also act on the airway cells, modifying secretory mechanisms which are important in mucosal defense. One hour after treatment, N-butyryl-homoserine lactone (C4-HL) had caused dilated extracellular spaces, loss of cilia, reduction of secretory material, and the presence of prenecrotic elements in the epithelium, while N-octanoyl-homoserine lactone (C8-HL) caused a mild lesion in the epithelium. After treatment with either C4- or C8-HL, reduced immunoreactivity was found using CC10 antibody. At ultrastructural examination, dilatation of the mitochondria was evident in ciliate and secretory cells, while solitary chemosensory cells appeared better preserved, showing aspects of nucleocytoplasmic activation. Using microarray analysis, we found down-regulation of early gene Fos and Egr1 in all AHL-treated specimens. In vivo pharmacological magnetic resonance imaging after C4- or C8-HL treatment showed a slight increase in tracheal secretion at a first evaluation 5 min after administration, with no increase in the following minutes. In conclusion, AHLs induce an early mucosal response, and the chondriomas of ciliate and secretory cells are the main cytological target of AHL action. Our results show that AHL action is not limited to activation of conspecific bacteria, but also modifies innate airway defense mechanisms. Anat Rec, 292:439-448, 2009. (C) 2009 WileyLiss, Inc.