Document Detail

Increased interstitial protein because of impaired lymph drainage does not induce fibrosis and inflammation in lymphedema.
MedLine Citation:
PMID:  23288156     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: The pathophysiology of lymphedema is incompletely understood. We asked how transcapillary fluid balance parameters and lymph flow are affected in a transgenic mouse model of primary lymphedema, which due to an inhibition of vascular endothelial growth factor receptor-3 (VEGFR-3) signaling lacks dermal lymphatics, and whether protein accumulation in the interstitium occurring in lymphedema results in inflammation.
METHODS AND RESULTS: As estimated using a new optical-imaging technique, we found that this signaling defect resulted in lymph drainage in hind limb skin of K14-VEGFR-3-Ig mice that was 34% of the corresponding value in wild-type. The interstitial fluid pressure and tissue fluid volumes were significantly increased in the areas of visible swelling only, whereas the colloid osmotic pressure in plasma, and thus the colloid osmotic pressure gradient, was reduced compared to wild-type mice. An acute volume load resulted in an exaggerated interstitial fluid pressure response in transgenic mice. There was no accumulation of collagen or lipid in skin, suggesting that chronic edema presented in the K14-VEGFR-3-Ig mouse was not sufficient to induce changes in tissue composition. Proinflammatory cytokines (interleukin-2, interleukin-6, interleukin-12) in subcutaneous interstitial fluid and macrophage infiltration in skin of the paw were lower, whereas the monocyte/macrophage cell fraction in blood and spleen was higher in transgenic compared with wild-type mice.
CONCLUSIONS: Our data suggest that a high interstitial protein concentration and longstanding edema is not sufficient to induce fibrosis and inflammation characteristic for the human condition and may have implications for our understanding of the pathophysiology of this condition.
C E Markhus; T V Karlsen; Marek Wagner; M Wagner; Ø S Svendsen; O Tenstad; K Alitalo; H Wiig
Related Documents :
22951726 - An alternative pathway of imiquimod-induced psoriasis-like skin inflammation in the abs...
20637096 - Mucopolysaccharidosis iiib, a lysosomal storage disease, triggers a pathogenic cns auto...
284076 - Human serum hexosaminidase: elevated b form isozyme in cancer patients.
6117076 - Isolation of a taxol-resistant chinese hamster ovary cell mutant that has an alteration...
56406 - Motheaten, an immunodeficient mutant of the mouse. ii. depressed immune competence and ...
24057186 - Effects of diethylhexyl phthalate (dehp) given neonatally on spermatogenesis of mice.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-03
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  33     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-17     Completed Date:  2013-03-14     Revised Date:  2013-07-01    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  266-74     Citation Subset:  IM    
Department of Biomedicine, University of Bergen, Norway.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Collagen / metabolism
Dermatitis, Allergic Contact / genetics,  immunology,  metabolism*,  pathology,  physiopathology
Disease Models, Animal
Extracellular Fluid / metabolism*
Inflammation Mediators / metabolism
Interleukin-12 / metabolism
Interleukin-2 / metabolism
Interleukin-6 / metabolism
Lymphatic Vessels / immunology,  metabolism*,  pathology,  physiopathology
Lymphedema / genetics,  immunology,  metabolism*,  pathology,  physiopathology
Macrophages / immunology
Mice, Inbred C57BL
Mice, Transgenic
Osmotic Pressure
Proteins / metabolism
Serum Albumin / metabolism
Skin / immunology,  metabolism*,  pathology,  physiopathology
Time Factors
Vascular Endothelial Growth Factor Receptor-3 / genetics,  metabolism
Water-Electrolyte Imbalance / immunology,  metabolism,  pathology
Reg. No./Substance:
0/Inflammation Mediators; 0/Interleukin-2; 0/Interleukin-6; 0/Proteins; 0/Serum Albumin; 187348-17-0/Interleukin-12; 9007-34-5/Collagen; EC Endothelial Growth Factor Receptor-3
Erratum In:
Arterioscler Thromb Vasc Biol. 2013 Jun;33(6):e119
Note: Wagner, M [corrected to Wagner, Marek]

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

Previous Document:  Subsequent Development of Fibroatheromas With Inflamed Fibrous Caps Can Be Predicted by Intracoronar...
Next Document:  Peptide inhibitor of CXCL4-CCL5 heterodimer formation, MKEY, inhibits experimental aortic aneurysm i...