Document Detail

Heme oxygenase-1 modulates thrombomodulin and activated protein C levels to attenuate lung injury in cecal ligation and puncture-induced acute lung injury mice.
MedLine Citation:
PMID:  22417130     Owner:  NLM     Status:  MEDLINE    
Acute lung injury (ALI) is often associated with sepsis and is the most common cause of acute respiratory failure. The authors evaluated the role of the heme oxygenase (HO)/carbon monoxide (CO) system on lung injury in a cecal ligation and puncture (CLP)-induced mouse model of ALI. The authors established CLP-induced ALI in C57BL/6 mice. They pretreated CLP-induced mice with HO-1 inducer (hemin) or HO-1 inhibitor (Zn protoporphyrin [Znpp]) and determined various lung injury parameters including partial pressure of arterial oxygen, thrombosis, edema, and plasma malondialdehyde (MDA), and myeloperoxidase (MPO) level. Enzyme-linked immunosorbent assay (ELISA) was performed to measure plasma thrombomodulin (TM) and activated protein C (APC) levels. TM and HO-1 expression in lung tissue was evaluated by immunofluorescence staining and Western blotting. Survival rate was also monitored. CLP-induced ALI was associated with decreased partial pressure of arterial oxygen, and increased thrombosis, edema, and plasma MDA, and MPO level. Plasma TM was significantly up-regulated, whereas cell surface TM in lung tissue was significantly decreased in the CLP group compared to the sham animals. Pretreatment with hemin caused up-regulation of HO-1 expression and improved partial pressure of arterial oxygen. Hemin pretreatment also caused a significant decrease in plasma TM along with increased cell surface TM expression in lung tissue, suggesting attenuation of lung injury. Survival data showed that no difference for survival between CLP animals pretreated with hemin or Znpp. Taken together, HO-1 exerts its protective effects on CLP-induced ALI via regulating cell surface TM and APC expression and modulating blood coagulation.
Dongsheng Fei; Xianglin Meng; Kai Kang; Chuanchuan Nan; Mingran Zhao; Shangha Pan; Meizhuo Gao; Songlin Yang; Mingyan Zhao
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-14
Journal Detail:
Title:  Experimental lung research     Volume:  38     ISSN:  1521-0499     ISO Abbreviation:  Exp. Lung Res.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-05     Completed Date:  2012-08-02     Revised Date:  2012-11-29    
Medline Journal Info:
Nlm Unique ID:  8004944     Medline TA:  Exp Lung Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  173-82     Citation Subset:  IM    
Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
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MeSH Terms
Acute Lung Injury / blood,  etiology,  metabolism*,  prevention & control
Enzyme Induction / drug effects
Enzyme Inhibitors / pharmacology
Heme Oxygenase-1 / antagonists & inhibitors,  biosynthesis,  metabolism*
Hemin / pharmacology
Lung / metabolism
Mice, Inbred C57BL
Protein C / metabolism*
Protoporphyrins / pharmacology
Sepsis / complications
Thrombomodulin / blood*
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Protein C; 0/Protoporphyrins; 0/THBD protein, mouse; 0/Thrombomodulin; 15442-64-5/zinc protoporphyrin; 16009-13-5/Hemin; EC Oxygenase-1

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