Document Detail


Targeted delivery of pulmonary arterial endothelial cells overexpressing interleukin-8 receptors attenuates monocrotaline-induced pulmonary vascular remodeling.
MedLine Citation:
PMID:  24790141     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Interleukin-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 RESULTS: The 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.
CONCLUSIONS: These provocative findings suggest that targeted delivery of ECs overexpressing IL8RA/B is effective in repairing the injured pulmonary vasculature.
Authors:
Jinyan Fu; Yiu-Fai Chen; Xiangmin Zhao; Judy R Creighton; Yuanyuan Guo; Fadi G Hage; Suzanne Oparil; Daisy D Xing
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2014-05-01
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  34     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-06-21     Completed Date:  2014-08-26     Revised Date:  2014-10-03    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1539-47     Citation Subset:  IM    
Copyright Information:
© 2014 American Heart Association, Inc.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Animals
Arterial Pressure
Cells, Cultured
Chemokine CCL2 / metabolism
Chemokines, CXC / metabolism
Disease Models, Animal
Endothelial Cells / metabolism,  pathology,  transplantation*
Female
Genetic Therapy / methods*
Genetic Vectors
Hypertension, Pulmonary / genetics,  metabolism,  pathology,  physiopathology,  prevention & control*
Hypertrophy, Right Ventricular / genetics,  metabolism,  physiopathology,  prevention & control
Macrophages / metabolism
Monocrotaline*
Neutrophil Infiltration
Neutrophils / metabolism
Nitric Oxide Synthase Type II / metabolism
Nitric Oxide Synthase Type III / metabolism
Ovariectomy
Pulmonary Artery / metabolism*,  pathology,  physiopathology
Rats
Rats, Sprague-Dawley
Receptors, Interleukin-8 / biosynthesis*,  genetics
Transduction, Genetic
Up-Regulation
Ventricular Function, Right
Ventricular Remodeling
Grant Support
ID/Acronym/Agency:
R01 HL044195/HL/NHLBI NIH HHS; R01 HL080017/HL/NHLBI NIH HHS; R01 HL116727/HL/NHLBI NIH HHS; R01HL087980/HL/NHLBI NIH HHS; R01HL116727/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Ccl2 protein, rat; 0/Chemokine CCL2; 0/Chemokines, CXC; 0/Gm1960 protein, rat; 0/Receptors, Interleukin-8; 73077K8HYV/Monocrotaline; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos2 protein, rat; EC 1.14.13.39/Nos3 protein, rat
Comments/Corrections
Comment In:
Arterioscler Thromb Vasc Biol. 2014 Jul;34(7):1336-8   [PMID:  24951651 ]

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