Analysis of pulmonary inflammation and function in the mouse and baboon after exposure to Mycoplasma pneumoniae CARDS toxin.
Analysis of pulmonary inflammation and function in the mouse and baboon after exposure to Mycoplasma pneumoniae CARDS toxin.
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DOI：
10.1371/journal.pone.0007562
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发表时间：
2009-10-27
期刊：
影响因子：
3.7
通讯作者：
Dube PH
中科院分区：
文献类型：
--
作者：
Hardy RD;Coalson JJ;Peters J;Chaparro A;Techasaensiri C;Cantwell AM;Kannan TR;Baseman JB;Dube PH
肺炎支原体产生一种ADP-核糖基化和空泡化毒素，称为共同体获得性呼吸窘迫综合征（Community Acquired Respiratory Distress Syndrome，简称ARDS）毒素，已证明其对组织和器官培养中的哺乳动物细胞具有细胞毒性。在这项研究中，我们测试的能力，重组肉毒杆菌毒素（肉毒杆菌毒素）引起的变化，在小鼠和狒狒的肺室。动物以剂量和活性依赖性方式通过增加促炎细胞因子IL-1α、1β、6、12、17、TNF-α和IFN-γ的表达对呼吸道暴露于rfos毒素作出反应。毒素暴露后，几种生长因子和趋化因子（包括KC、IL-8、RANTES和G-CSF）也呈剂量依赖性增加。仅在狒狒中观察到IFN-γ表达增加;否则，小鼠和狒狒以非常相似的方式对肉毒毒素作出反应。向小鼠或狒狒的气道引入肉毒毒素导致细胞炎症反应，其特征为剂量依赖性早期空泡化和细支气管上皮细胞毒性，随后是强烈的支气管周围和血管周围淋巴细胞浸润。在小鼠中，毒素暴露两天后，毒素引起气道高反应性以及长期气道阻塞。气道功能、细胞因子表达和细胞炎症的变化在时间上相关，并且与M.肺炎感染。总之，这些数据表明，肉毒毒素广泛地与肺隔室相互作用，并且肉毒毒素足以引起长期的炎症反应和气道功能障碍。
Mycoplasma pneumoniae produces an ADP-ribosylating and vacuolating toxin known as the CARDS (Community Acquired Respiratory Distress Syndrome) toxin that has been shown to be cytotoxic to mammalian cells in tissue and organ culture. In this study we tested the ability of recombinant CARDS (rCARDS) toxin to elicit changes within the pulmonary compartment in both mice and baboons. Animals responded to a respiratory exposure to rCARDS toxin in a dose and activity-dependent manner by increasing the expression of the pro-inflammatory cytokines IL-1α, 1β, 6, 12, 17, TNF-α and IFN-γ. There was also a dose-dependent increase in several growth factors and chemokines following toxin exposure including KC, IL-8, RANTES, and G-CSF. Increased expression of IFN-γ was observed only in the baboon; otherwise, mice and baboons responded to CARDS toxin in a very similar manner. Introduction of rCARDS toxin to the airways of mice or baboons resulted in a cellular inflammatory response characterized by a dose-dependent early vacuolization and cytotoxicity of the bronchiolar epithelium followed by a robust peribronchial and perivascular lymphocytic infiltration. In mice, rCARDS toxin caused airway hyper-reactivity two days after toxin exposure as well as prolonged airway obstruction. The changes in airway function, cytokine expression, and cellular inflammation correlate temporally and are consistent with what has been reported for M. pneumoniae infection. Altogether, these data suggest that the CARDS toxin interacts extensively with the pulmonary compartment and that the CARDS toxin is sufficient to cause prolonged inflammatory responses and airway dysfunction.
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影响因子：
3.1
作者：
Bubeck, Sarah S.;Cantwell, Angelene M.;Dube, Peter H.
通讯作者：
Dube, Peter H.
DOI：
10.1164/ajrccm.156.3.9606031
发表时间：
1997-09-01
影响因子：
24.7
作者：
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作者：
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DOI：
10.1164/rccm.200209-996oc
发表时间：
2003-02-01
影响因子：
24.7
作者：
Lieberman, D;Lieberman, D;Boldur, I
通讯作者：
Boldur, I
DOI：
10.1073/pnas.0510644103
发表时间：
2006-04-25
影响因子：
11.1
作者：
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通讯作者：
Baseman, JB