title: Is there a role of TNFR1 in acute lung injury cases associated with extracorporeal circulation?
abstract: The signaling pathway for tumor necrosis factor-α (TNF-α) and its receptors is up-regulated during extracorporeal circulation (ECC), and recruits blood neutrophil into the lung tissue, which results in acute lung injury (ALI). In this study, we evaluated the role of tumor necrosis factor receptor 1 (TNFR1) in ECC-induced ALI by blocking TNF-α binding to TNFR1 with CAY10500. Anesthetized Sprague-Dawley (SD) rats were pretreated intravenously with phosphate buffered saline (PBS) or vehicle (0.3 ml ethanol IV) or CAY10500, and then underwent ECC for 2 h. The oxygenation index (OI) and pulmonary inflammation were assessed after ECC. OI was significantly decreased, while TNF-α and neutrophil in bronchoalveolar lavage fluid (BALF) and plasma TNF-α increased after ECC. Pretreatment of CAY10500 decreased plasma TNF-α level, but did not decrease TNF-α levels and neutrophil counts in BALF or improve OI. Lung histopathology showed significant alveolar congestion, infiltration of the leukocytes in the airspace, and increased thickness of the alveolar wall in all ECC-treated groups. CAY10500 pretreatment slightly reduced leukocyte infiltration in lungs, but did not change the wet/dry ratio in the lung tissue. Blocking TNF-α binding to TNFR1 by CAY10500 intravenously slightly mitigates pulmonary inflammation, but cannot improve the pulmonary function, indicating the limited role of TNFR1 pathway in circulating inflammatory cell in ECC-induced ALI.
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Chong-wei
authors.initials: CW
authors.lastname: Zhang
authors.forename: Wen-jing
authors.initials: WJ
authors.lastname: Zhou
authors.forename: Jiao
authors.initials: J
authors.lastname: Chen
authors.forename: Nan-fu
authors.initials: NF
authors.lastname: Luo
authors.forename: Li-na
authors.initials: LN
authors.lastname: Gong
authors.forename: Lei
authors.initials: L
authors.lastname: Du
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D005112:Extracorporeal Circulation / Q000009:adverse effects*; D006651:Histocytochemistry; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha