Is there a role of TNFR1 in acute lung injury cases associated with extracorporeal circulation

• Published in: Journal of Zhejiang University. B. Science 2014-03, Vol.15 (3), p.281-288
• Main Authors: Zhao, Yu, Zhang, Chong-wei, Zhou, Wen-jing, Chen, Jiao, Luo, Nan-fu, Gong, Li-na, Du, Lei, Zhou, Jing
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - immunology; Animals; Biomedical and Life Sciences; Biomedicine; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Extracorporeal Circulation - adverse effects; Histocytochemistry; Male; Neutrophils - immunology; Pneumonia - immunology; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, Tumor Necrosis Factor, Type I - immunology; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - immunology
• ISSN: 1673-1581; 1862-1783
• DOI: 10.1631/jzus.B1300147

The signaling pathway for tumor necrosis factor-a （TNF-a） and its receptors is up-regulated during ex- tracorporeal circulation （ECC）, and recruits blood neutrophil into the lung tissue, which results in acute lung injury （ALl） In this study, we evaluated the role of tumor necrosis factor receptor I （TNFR1） in ECC-induced ALl by blocking TNF-a binding to TNFR1 with CAY10500. Anesthetized Sprague-Dawley （SD） rats were pretreated intravenously with phos- phate buffered saline （PBS） or vehicle （0.3 ml ethanol IV） or CAY10500, and then underwent ECC for 2 h. The oxy- genation index （OI） and pulmonary inflammation were assessed after ECC. OI was significantly decreased, while TNF-a and neutrophil in bronchoalveolar lavage fluid （BALF） and plasma TNF-a increased after ECC. Pretreatment of CAY10500 decreased plasma TNF-a level, but did not decrease TNF-a 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-a 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 ALl.