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: Chou-Chin Lan, Chung-Kan Peng, Shih-En Tang, Shu-Yu Wu, Kun-Lun Huang, Chin-Pyng Wu
• Journal: PloS one (PLoS One) Vol. 11 Issue 8 Pg. e0159922 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 27513332 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Cytokines
• NF-kappa B
• Vascular Endothelial Growth Factor A
• Extracellular Signal-Regulated MAP Kinases

Topics

• Acute Lung Injury (etiology, metabolism, pathology, prevention & control)
• Animals
• Antibodies, Monoclonal (pharmacology)
• Capillary Permeability (drug effects)
• Cytokines (metabolism)
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
• Gene Expression Regulation (drug effects)
• Inflammation (etiology, metabolism, pathology, prevention & control)
• Male
• NF-kappa B (antagonists & inhibitors, metabolism)
• Pulmonary Edema (etiology, metabolism, pathology, prevention & control)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (complications)
• Signal Transduction (drug effects)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, metabolism)