Document Detail


A novel liposome-based therapy to reduce complement-mediated injury in revascularized tissues.
MedLine Citation:
PMID:  21074780     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Ischemia/reperfusion (IR) injury is an unavoidable consequence of tissue transplantation or replantation that often leads to inflammation and cell death. Excessive complement activation following IR induces endothelial cell injury, altering vascular and endothelial barrier function causing tissue dysfunction. To mitigate the IR response, various systemic anti-complement therapies have been tried. Recently, we developed a localized therapy that uses biotinylated fusogenic lipid vesicles (BioFLVs) to first incorporate biotin tethers onto cell membranes, which are then used to bind therapeutic fusion proteins containing streptavidin (SA) resulting in the decoration of cell membranes. The therapy is applied in two steps using solutions delivered intra-arterially.
MATERIALS AND METHODS: Alteration of formulation, concentration and duration of incubation of BioFLVs were conducted to demonstrate the ability of the system to modulate biotin tether incorporation in cultured cells. Using a rat hind limb model, the ability of BioFLVs to decorate endothelium of femoral vessels with FITC-labeled SA for 48 h of reperfusion was demonstrated. The feasibility of a BioFLV-based anti-complement therapy was tested in cultured cells using SA fused with vaccinia virus complement control protein (SA-VCP), a C3 convertase inhibitor. Human ovarian carcinoma (SKOV-3) cells were incubated with BioFLVs first and then with SA-VCP. To activate complement the cells were treated with a SKOV-3-specific antibody (trastuzumab) and incubated in human serum.
RESULTS: Decoration of cells with SA-VCP effectively reduced complement deposition.
CONCLUSIONS: We conclude that BioFLV-mediated decoration of cell membranes with anti-complement proteins reduces complement activation and deposition in vitro and has the potential for application against inappropropriate complement activation in vivo.
Authors:
Ledia Goga; Sathnur B Pushpakumar; Gustavo Perez-Abadia; Paul Olson; Gary Anderson; Chirag V Soni; John H Barker; Claudio Maldonado
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-16
Journal Detail:
Title:  The Journal of surgical research     Volume:  165     ISSN:  1095-8673     ISO Abbreviation:  J. Surg. Res.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-01-11     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e51-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky 40292, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Biotinylation*
Cells, Cultured
Complement Pathway, Classical
Complement System Proteins / physiology*
Endothelium, Vascular / metabolism
Humans
Liposomes / administration & dosage*
Male
Rats
Rats, Inbred F344
Reperfusion Injury / prevention & control*
Grant Support
ID/Acronym/Agency:
R41 HL079855-01/HL/NHLBI NIH HHS; R41HL079855/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Liposomes; 9007-36-7/Complement System Proteins
Comments/Corrections

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


Previous Document:  Unpaired extinction: implications for treating post-traumatic stress disorder.
Next Document:  Effects of Platelet-Rich Plasma on Intestinal Anastomotic Healing in Rats: PRP Concentration is a Ke...