Peptide XIB13 reduces capillary leak in a rodent burn model.
OBJECTIVE
Edema due to capillary leak is a generalized and life threatening event in sepsis and major burns for which there is no causal treatment. Local burn wounds are an ideal model to investigate the impact of a new therapeutic agent on edema formation. We aimed to identify peptide sequences of cingulin that can attenuate stress-induced endothelial cytoskeleton disarrangement in vitro and which reduce burn-induced edema in vivo.


METHODS
Cingulin-derived peptides were screened in high content cell culture assays monitoring actin displacement and endothelial cell/cell contacts. The ears of male hairless mice (n=44) were inflicted with full thickness burns using a hot air jet. Mice with and without burn injuries were treated with Xib13 or solvent by continuous intraperitoneal application for 3 days. Edema, microcirculation, leukocyte-endothelial interactions and angiogenesis - measured as non-perfused area - were investigated over a 12-day period using intravital fluorescence microscopy.


RESULTS
Xib13 reduced endothelial stress formation and stabilized endothelial tight junctions in cell-cultures. In the burn model, Xib13 improved angiogenesis compared to controls (non-perfused area on day 12: 5.7±1.5% vs. 12.0±2.1%; p<0.05). Edema was significantly reduced at all observation points in Xib13-treated animals as compared to controls (day 12: 67.6±2.6% vs. 83.2±6.4%).


CONCLUSIONS
Xib13 improved angiogenesis, reduced edema formation and showed no side effects on other physiological parameters. Since edema formation is a serious parameter for burn conversion and is associated with survival it could provide a new treatment option for patients with burn injuries.
Department of Plastic and Hand Surgery, Burn Center, BG-University Hospital Bergmannsheil, Ruhr University Bochum, Germany. Electronic address: ole.goertz@rub.de.
Ole
O
Goertz
Department of Plastic and Hand Surgery, Burn Center, BG-University Hospital Bergmannsheil, Ruhr University Bochum, Germany.
Henrik
H
Lauer
Department of Plastic and Hand Surgery, Burn Center, BG-University Hospital Bergmannsheil, Ruhr University Bochum, Germany.
Leon
L
von der Lohe
Department of Plastic and Hand Surgery, Burn Center, BG-University Hospital Bergmannsheil, Ruhr University Bochum, Germany.
Marcus
M
Lehnhardt
Skin & Endothelium Research Division (SERD), Department of Dermatology, Medical University Vienna, Austria.
Klaudia
K
Schossleitner
Skin & Endothelium Research Division (SERD), Department of Dermatology, Medical University Vienna, Austria.
Max
M
Petzelbauer
Skin & Endothelium Research Division (SERD), Department of Dermatology, Medical University Vienna, Austria. Electronic address: Peter.Petzelbauer@meduniwien.ac.at.
Peter
P
Petzelbauer
D000818:Animals; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002196:Capillaries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects*; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004487:Edema / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology*; D008812:Mice, Hairless; D008833:Microcirculation / Q000187:drug effects; D008840:Microfilament Proteins / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D022502:Stress Fibers / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects
C061407:CGN protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; C000595057:glycyl-arginyl-arginyl-prolyl-leucyl-glycyl-glycyl-isoleucyl-seryl-glycyl-glycine