title: Anti-Vascular Endothelial Growth Factor Antibody Suppresses ERK and NF-κB Activation in Ischemia-Reperfusion Lung Injury.
abstract: Ischemia-reperfusion (IR)-induced acute lung injury (ALI) is implicated in several clinical conditions like lung transplantation, acute pulmonary embolism after thrombolytic therapy, re-expansion of collapsed lung from pneumothorax or pleural effusion, cardiopulmonary bypass and etc. Because mortality remains high despite advanced medical care, prevention and treatment are important clinical issues for IR-induced ALI. Vascular endothelial growth factor (VEGF) has a controversial role in ALI. We therefore conducted this study to determine the effects of anti-VEGF antibody in IR-induced ALI. In the current study, the IR-induced ALI was conducted in a rat model of isolated-perfused lung in situ in the chest. The animals were divided into the control, control + preconditioning anti-VEGF antibody (bevacizumab, 5mg/kg), IR, IR + preconditioning anti-VEGF antibody (1mg/kg), IR+ preconditioning anti-VEGF antibody (5mg/kg) and IR+ post-IR anti-VEGF antibody (5mg/kg) group. There were eight adult male Sprague-Dawley rats in each group. The IR caused significant pulmonary micro-vascular hyper-permeability, pulmonary edema, neutrophilic infiltration in lung tissues, increased tumor necrosis factor-α, and total protein concentrations in bronchoalveolar lavage fluid. VEGF and extracellular signal-regulated kinase (ERK) were increased in IR-induced ALI. Administration of preconditioning anti-VEGF antibody significantly suppressed the VEGF and ERK expressions and attenuated the IR-induced lung injury. This study demonstrates the important role of VEGF in early IR-induced ALI. The beneficial effects of preconditioning anti-VEGF antibody in IR-induced ALI include the attenuation of lung injury, pro-inflammatory cytokines, and neutrophilic infiltration into the lung tissues.
authors: Division of Pulmonary Medicine, Buddhist Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan.|School of Medicine, Tzu-Chi University, Hualien, Taiwan.
authors: Chou-Chin
authors: CC
authors: Lan
authors: Division of Pulmonary Medicine, Tri-Service General Hospital, Taipei, Taiwan.|Institute of Undersea and Hyperbaric Medicine, National Defense Medical Center, Taipei, Taiwan.
authors: Chung-Kan
authors: CK
authors: Peng
authors: Division of Pulmonary Medicine, Tri-Service General Hospital, Taipei, Taiwan.|Institute of Undersea and Hyperbaric Medicine, National Defense Medical Center, Taipei, Taiwan.
authors: Shih-En
authors: SE
authors: Tang
authors: Institute of Undersea and Hyperbaric Medicine, National Defense Medical Center, Taipei, Taiwan.
authors: Shu-Yu
authors: SY
authors: Wu
authors: Division of Pulmonary Medicine, Tri-Service General Hospital, Taipei, Taiwan.|Institute of Undersea and Hyperbaric Medicine, National Defense Medical Center, Taipei, Taiwan.
authors: Kun-Lun
authors: KL
authors: Huang
authors: Department of Critical Care Medicine, Li-Shin Hospital, Tao-Yuan County, Taiwan.
authors: Chin-Pyng
authors: CP
authors: Wu
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; D048049:Extracellular Signal-Regulated MAP Kinases