Document Detail


Cellular and molecular mechanisms of venous leg ulcers development--the "puzzle" theory.
MedLine Citation:
PMID:  20224526     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This review presents a hypothetical model of the development of a venous leg ulcer. The primary pathology is venous hypertension that leads to increased capillary permeability, resulting in extravasation of erythrocytes. Macrophages produce proinflammatory cytokines, which enhance the expression of adhesion molecules in the endothelium of postcapillary venules and increase the recruitment of leukocytes to the pericapillary interstitium. Extravasated T lymphocytes stimulated by cytokines, which are produced by activated macrophages, differentiate toward the Th1 phenotype. In the case of excessive extracapillary passage of erythrocytes or impaired transport of ferric ions by macrophages, the accumulation of iron in the dermis can occur. In tissues with a high concentration of iron, T lymphocytes proliferate instead of undergoing apoptosis. This is possible due to the internalization of the INF-gR2 chain of the interferon-g receptor, the downregulation of inducible nitric oxide synthase expression in macrophages and the inactivation of the active site of caspases. Stimulated by interferon-g skin keratinocytes produce chemokines: CXCL9, CXCL10 and CXCL11, which attract T lymphocytes. Finally, positive feedback loops develop resulting in the migration of T lymphocytes toward the epidermis and in high local concentrations of interferon-g and keratinocyte-derived chemokines. T lymphocytes invading epidermis produce interferon-g and Fas ligand. High concentrations of interferon-g result in the overexpression of Fas by keratinocytes. Matrix metalloproteinases shed Fas ligand from T lymphocytes. The combined effect of Fas ligand and interferon-g on Fas-overexpressing keratinocytes results in their abundant apoptosis and dermo-epidermal detachment, which is clinically manifested as blister-like lesions that progress to chronic ulcerations.
Authors:
M Simka
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  International angiology : a journal of the International Union of Angiology     Volume:  29     ISSN:  1827-1839     ISO Abbreviation:  Int Angiol     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-03-12     Completed Date:  2010-07-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8402693     Medline TA:  Int Angiol     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  1-19     Citation Subset:  IM    
Affiliation:
Department of Angiology, Private Healthcare Institution SANA, Pszczyna, Poland. mariansimka@poczta.onet.pl
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Capillary Permeability*
Chemotaxis
Cytokines / immunology
Disease Progression
Endothelium, Vascular / immunology
Erythrocytes / immunology*,  metabolism,  pathology
Humans
Inflammation Mediators / immunology
Iron / metabolism
Keratinocytes / immunology,  pathology
Macrophages / immunology
Risk Factors
T-Lymphocytes / immunology*,  metabolism
Varicose Ulcer / etiology*,  immunology,  metabolism,  pathology,  physiopathology
Venous Pressure*
Chemical
Reg. No./Substance:
0/Cytokines; 0/Inflammation Mediators; 7439-89-6/Iron

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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