title: Heme oxygenase-1 modulates thrombomodulin and activated protein C levels to attenuate lung injury in cecal ligation and puncture-induced acute lung injury mice.
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.
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Fei
authors.forename: Xianglin
authors.initials: X
authors.lastname: Meng
authors.forename: Kai
authors.initials: K
authors.lastname: Kang
authors.forename: Chuanchuan
authors.initials: C
authors.lastname: Nan
authors.forename: Mingran
authors.initials: M
authors.lastname: Zhao
authors.forename: Shangha
authors.initials: S
authors.lastname: Pan
authors.forename: Meizhuo
authors.initials: M
authors.lastname: Gao
authors.forename: Songlin
authors.initials: S
authors.lastname: Yang
authors.forename: Mingyan
authors.initials: M
authors.lastname: Zhao
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D000818:Animals; D002432:Cecum; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D008026:Ligation; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011486:Protein C / Q000378:metabolism*; D011524:Protoporphyrins / Q000494:pharmacology; D011677:Punctures; D018805:Sepsis / Q000150:complications; D018180:Thrombomodulin / Q000097:blood*
chemical_list: D004791:Enzyme Inhibitors; D011486:Protein C; D011524:Protoporphyrins; C569169:THBD protein, mouse; D018180:Thrombomodulin; C017803:zinc protoporphyrin; D006427:Hemin; D051547:Heme Oxygenase-1