• Jinyan Fu, Yiu-Fai Chen, Xiangmin Zhao, Judy R Creighton, Yuanyuan Guo, Fadi G Hage, Suzanne Oparil, and Daisy D Xing.
• From the Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine (J.F., Y.-F.C., X.Z., Y.G., F.G.H., S.O., D.D.X.) and Department of Anesthesiology, University of Alabama at Birmingham (J.R.C.); Department of Biochemistry and the Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Xinjiang, China (J.F.); and Section of Cardiology, Birmingham Veteran's Administration Medical Center, AL (F.G.H.).
• Arterioscler. Thromb. Vasc. Biol. 2014 Jul 1; 34 (7): 1539-47.

ObjectiveInterleukin-8 (IL-8) receptors IL8RA and IL8RB (IL8RA/B) on neutrophil membranes bind to IL-8 with high affinity and play a critical role in neutrophil recruitment to sites of injury and inflammation. This study tested the hypothesis that administration of rat pulmonary arterial endothelial cells (ECs) overexpressing IL8RA/B can accelerate the adhesion of ECs to the injured lung and inhibit monocrotaline-induced pulmonary inflammation, arterial thickening and hypertension, and right ventricular hypertrophy.Approach And ResultsThe treatment groups included 10-week-old ovariectomized Sprague-Dawley rats that received subcutaneous injection of PBS (vehicle), a single injection of monocrotaline (monocrotaline alone, 60 mg/kg, SC), monocrotaline followed by intravenous transfusion of ECs transduced with the empty adenoviral vector (null-EC), and monocrotaline followed by intravenous transfusion of ECs overexpressing IL8RA/B (1.5 × 10(6) cells/rat). Two days or 4 weeks after monocrotaline treatment, endothelial nitric oxide synthase, inducible nitric oxide synthase, cytokine-induced neutrophil chemoattractant-2β (IL-8 equivalent in rat), and monocyte chemoattractant protein-1 expression, neutrophil and macrophage infiltration into pulmonary arterioles, and arteriolar and alveolar morphology were measured by histological and immunohistochemical techniques. Proinflammatory cytokine/chemokine protein levels were measured by Multiplex rat-specific magnetic bead-based sandwich immunoassay in total lung homogenates. Transfusion of ECs overexpressing IL8RA/B significantly reduced monocrotaline-induced neutrophil infiltration and proinflammatory mediator (IL-8, monocyte chemoattractant protein-1, inducible nitric oxide synthase, cytokine-induced neutrophil chemoattractant, and macrophage inflammatory protein-2) expression in lungs and pulmonary arterioles and alveoli, pulmonary arterial pressure, and pulmonary arterial and right ventricular hypertrophy and remodeling.ConclusionsThese provocative findings suggest that targeted delivery of ECs overexpressing IL8RA/B is effective in repairing the injured pulmonary vasculature.© 2014 American Heart Association, Inc.

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