Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth.
Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth.
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DOI：
10.1126/scitranslmed.3000928
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发表时间：
2010-04-28
影响因子：
17.1
通讯作者：
Welsh MJ
中科院分区：
文献类型：
--
作者：
Stoltz DA;Meyerholz DK;Pezzulo AA;Ramachandran S;Rogan MP;Davis GJ;Hanfland RA;Wohlford-Lenane C;Dohrn CL;Bartlett JA;Nelson GA 4th;Chang EH;Taft PJ;Ludwig PS;Estin M;Hornick EE;Launspach JL;Samuel M;Rokhlina T;Karp PH;Ostedgaard LS;Uc A;Starner TD;Horswill AR;Brogden KA;Prather RS;Richter SS;Shilyansky J;McCray PB Jr;Zabner J;Welsh MJ
肺部疾病导致囊性纤维化 (CF) 的大部分发病和死亡。然而，由于缺乏具有 CF 特征的动物模型，对其发病机制的理解受到了阻碍。为了克服这个问题，我们最近培育出了带有靶向 CFTR 基因的猪。我们现在报告说，在出生后几个月内，CF 猪自发地出现 CF 肺部疾病的标志性特征，包括气道炎症、重塑、粘液积聚和感染。它们的肺部含有多种细菌，表明宿主防御缺陷存在均等机会。在人类中，炎症和感染之间的时间和因果关系仍然不确定。为了研究这些过程，我们研究了新生猪。他们的肺部没有表现出炎症，但与对照组相比，无菌情况较少。此外，在肺内细菌攻击后，CF猪未能像野生型猪那样有效地根除细菌。这些结果表明，细菌消除受损是引发CF肺部一系列炎症和病理的致病事件。发现 CF 猪在出生后数小时内存在细菌宿主防御缺陷，为进一步研究发病机制并在继发后果出现之前测试治疗和预防策略提供了机会。
Lung disease causes most of the morbidity and mortality in cystic fibrosis (CF). However, understanding its pathogenesis has been hindered by lack of an animal model with characteristic features of CF. To overcome this problem, we recently generated pigs with targeted CFTR genes. We now report that, within months of birth, CF pigs spontaneously develop hallmark features of CF lung disease including airway inflammation, remodeling, mucus accumulation, and infection. Their lungs contained multiple bacterial species, suggesting an equal opportunity host defense defect. In humans, the temporal and causal relationships between inflammation and infection have remained uncertain. To investigate these processes, we studied newborn pigs. Their lungs showed no inflammation, but were less often sterile than controls. Moreover, after intrapulmonary bacterial challenge, CF pigs failed to eradicate bacteria as effectively as wild-type pigs. These results suggest that impaired bacterial elimination is the pathogenic event that initiates a cascade of inflammation and pathology in CF lungs. Finding that CF pigs have a bacterial host defense defect within hours of birth provides an opportunity to further investigate pathogenesis and to test therapeutic and preventive strategies before secondary consequences develop.
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影响因子：
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作者：
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