NDLI: Heme oxygenase-1 modulates thrombomodulin and activated protein C levels to attenuate lung injury in cecal ligation and puncture-induced acute lung injury mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Fei, Dongsheng Meng, Xianglin Kang, Kai Nan, Chuanchuan Zhao, Mingran Pan, Shangha Gao, Meizhuo Yang, Songlin Zhao, Mingyan
Description	Country affiliation: China Author Affiliation: Fei D ( Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, China.)
Abstract	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.
File Format	HTM / HTML
ISSN	01902148
Issue Number	4
Volume Number	38
e-ISSN	15210499
Journal	Experimental Lung Research
Language	English
Publisher	Taylor & Francis
Publisher Date	2012-05-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Discipline Pulmonary Medicine Acute Lung Injury Metabolism Heme Oxygenase-1 Protein C Thrombomodulin Blood Etiology Prevention & Control Animals Cecum Enzyme Induction Drug Effects Enzyme Inhibitors Pharmacology Antagonists & Inhibitors Biosynthesis Hemin Ligation Lung Male Mice Mice, Inbred C57bl Protoporphyrins Punctures Sepsis Complications Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Pulmonary and Respiratory Medicine Molecular Biology Clinical Biochemistry

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