期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep32109
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资金
- Japan Society for the Promotion of Science
- Foundation for Dietary Scientific Research
- Cardiovascular Research Fund
- Kurozumi Medical Foundation
- Naito Foundation
- Suzuken Memorial Foundation
- Takeda Science Foundation
- Nipponham Foundation
- Sapporo Bioscience Foundation
- Japan Foundation for Pediatric Research
- Grants-in-Aid for Scientific Research [15J10795] Funding Source: KAKEN
Thromboxane A(2) (TXA(2)) is produced in the lungs of patients suffering from acute lung injury (ALI). We assessed its contribution in disease progression using three different ALI mouse models. The administration of hydrochloric acid (HCl) or oleic acid (OA)+ lipopolysaccharide (LPS) caused tissue edema and neutrophil infiltration with TXA(2) production in the lungs of the experimental mice. The administration of LPS induced only neutrophil accumulation without TXA(2) production. Pretreatment with T prostanoid receptor (TP) antagonist attenuated the tissue edema but not neutrophil infiltration in these models. Intravital imaging and immunostaining demonstrated that administration of TP agonist caused vascular hyper-permeability by disrupting the endothelial barrier formation in the mouse ear. In vitro experiments showed that TP-stimulation disrupted the endothelial adherens junction, and it was inhibited by Ca2+ channel blockade or Rho kinase inhibition. Thus endogenous TXA(2) exacerbates ALI, and its blockade attenuates it by modulating the extent of lung edema. This can be explained by the endothelial hyper-permeability caused by the activation of TXA(2)-TP axis, via Ca2+- and Rho kinase-dependent signaling.
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