Aging exacerbates acute lung injury-induced changes of the air-blood barrier, lung function, and inflammation in the mouse

被引:61
作者
Kling, Katharina Maria [1 ,2 ]
Lopez-Rodriguez, Elena [1 ,2 ]
Pfarrer, Christiane [3 ]
Muehlfeld, Christian [1 ,2 ,4 ]
Brandenberger, Christina [1 ,2 ,4 ]
机构
[1] Hannover Med Sch, Inst Funct & Appl Anat, Hannover, Germany
[2] German Ctr Lung Res DZL, Biomed Res Endstage & Obstruct Lung Dis Hannover, Hannover, Germany
[3] Univ Vet Med Hannover, Dept Anat, Hannover, Germany
[4] Cluster Excellence Regenerat Biol Reconstruct The, Hannover, Germany
关键词
acute lung injury; aging; air-blood barrier; lung function; neutrophilic inflammation; TIGHT JUNCTION; MATRIX METALLOPROTEINASES; NEUTROPHIL ELASTASE; PULMONARY; ACTIVATION; DYSREGULATION; MECHANISMS; PERMEABILITY; STEREOLOGY; INHIBITORS;
D O I
10.1152/ajplung.00347.2016
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Acute lung injury (ALI) is characterized by hypoxemia, enhanced permeability of the air-blood barrier, and pulmonary edema. Particularly in the elderly, ALI is associated with increased morbidity and mortality. The reasons for this, however, are poorly understood. We hypothesized that age-related changes in pulmonary structure, function, and inflammation lead to a worse prognosis in ALI. ALI was induced in young (10 wk old) and old (18 mo old) male C57BL/6 mice by intranasal application of 2.5 mg lipopolysaccharide (LPS)/kg body wt or saline (control mice). After 24 h, lung function was assessed, and lungs were either processed for stereological or inflammatory analysis, such as bronchoalveolar lavage fluid (BALF) cytometry and qPCR. Both young and old mice developed severe signs of ALI, including alveolar and septal edema and enhanced inflammatory BALF cells. However, the pathology of ALI was more pronounced in old compared with young mice with nearly sixfold higher BALF protein concentration, twice the number of neutrophils, and significantly higher expression of neutrophil chemokine Cxcl1, adhesion molecule Icam-1, and metalloprotease-9, whereas the expression of tight junction protein occludin significantly decreased. The old LPS mice had thicker alveolar septa attributable to higher volumes of interstitial cells and extracellular matrix. Tissue resistance and elastance reflected observed changes at the ultrastructural level in the lung parenchyma in ALI of young and old mice. In summary, the pathology of ALI with advanced age in mice is characterized by a greater neutrophilic inflammation, leakier air-blood barrier, and altered lung function, which is in line with findings in elderly patients.
引用
收藏
页码:L1 / L12
页数:12
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