Document Detail


Perivascular T-cell infiltration leads to sustained pulmonary artery remodeling after endothelial cell damage.
MedLine Citation:
PMID:  20813993     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pulmonary hypertension is a vascular proliferative disease characterized by pulmonary artery remodeling because of dysregulated endothelial and smooth muscle cell proliferation. Although the role of inflammation in the development of the disease is not well-defined, plexogenic lesions in human disease are characterized by perivascular inflammation composed, in part, of T cells. We explored the role of T-cell infiltration on pulmonary vascular remodeling after endothelial cell damage. We induced endothelial cell damage using monocrotaline and isolated the role of T cells by using Rag1(tm1Mom) mice and performing adoptive T-cell transfer. We found that monocrotaline causes pulmonary vascular endothelial cell injury followed by a perivascular inflammatory response. The infiltration of inflammatory cells primarily involves CD4(+) T cells and leads to the progressive muscularization of small (<30 μm) arterioles. Pulmonary vascular proliferative changes were accompanied by progressive and persistent elevations in right ventricular pressure and right ventricular hypertrophy. Supporting the central role of CD4(+) T cells in the inflammatory response, Rag1(tm1Mom) (Rag1(-/-)) mice, which are devoid of T and B cells, were protected from the development of vascular injury when exposed to monocrotaline. The introduction of T cells from control mice into Rag1(-/-) mice reproduced the vascular injury phenotype. These data indicate that after endothelial cell damage, CD4(+) T-cell infiltration participates in pulmonary vascular remodeling. This finding suggests that a CD4(+) T-cell immune response may contribute to the pathogenesis of inflammatory vascular lesions seen in some forms of pulmonary hypertension.
Authors:
Michael J Cuttica; Thomas Langenickel; Audrey Noguchi; Roberto F Machado; Mark T Gladwin; Manfred Boehm
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Publication Detail:
Type:  Journal Article     Date:  2010-09-02
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  45     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-13     Completed Date:  2011-09-08     Revised Date:  2013-03-28    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  62-71     Citation Subset:  IM    
Affiliation:
Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Drive, MSC1454, Building 10-CRC, Room 5 East 3132, Bethesda, MD 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Adoptive Transfer
Animals
CD4-Positive T-Lymphocytes / immunology*,  metabolism,  pathology,  transplantation
Endothelial Cells / immunology*,  metabolism,  pathology
Homeodomain Proteins / genetics,  immunology,  metabolism
Humans
Hypertension, Pulmonary / genetics,  immunology*,  pathology,  physiopathology
Inflammation / genetics,  immunology,  metabolism,  pathology,  physiopathology
Mice
Mice, Knockout
Muscle, Smooth, Vascular
Pulmonary Artery / immunology*,  metabolism,  pathology,  physiopathology
Chemical
Reg. No./Substance:
0/Homeodomain Proteins; 128559-51-3/RAG-1 protein
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