Leukocyte-endothelial cell interaction is necessary for photodynamic therapy induced vascular permeabilization.

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State: Public
Version: author
Serval ID
serval:BIB_9535E85BB1E8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Leukocyte-endothelial cell interaction is necessary for photodynamic therapy induced vascular permeabilization.
Journal
Lasers In Surgery and Medicine
Author(s)
Debefve E., Mithieux F., Perentes J.Y., Wang Y., Cheng C., Schaefer S.C., Ruffieux C., Ballini J.P., Gonzalez M., van den Bergh H., Ris H.B., Lehr H.A., Krueger T.
ISSN
1096-9101 (Electronic)
ISSN-L
0196-8092
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
43
Number
7
Pages
696-704
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish. PDF type: Original article
Abstract
BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) affects vascular barrier function and thus increases vessel permeability. This phenomenon may be exploited to facilitate targeted drug delivery and may lead to a new clinical application of photodynamic therapy. Here, we investigate the role of leukocyte recruitment for PDT-induced vascular permeabilization.
STUDY DESIGN/MATERIAL AND METHODS: Fluorescein isothiocyanate dextran (FITC-D, 2,000 kDa) was injected intravenously 120 minutes after focal PDT on striated muscle in nude mice bearing dorsal skinfold chambers (Visudyne® 800 µg/kg, fluence rate 300 mW/cm2 , light dose of 200 J/cm2). Leukocyte interaction with endothelial cells was inhibited by antibodies functionally blocking adhesion molecules ("MABS-PDT" group, n = 5); control animals had PDT but no antibody injection (group "PDT", n = 7). By intravital microscopy, we monitored leukocyte rolling and sticking in real-time before, 90 and 180 minutes after PDT. The extravasation of FITC-D from striated muscle vessels into the interstitial space was determined in vivo during 45 minutes to assess treatment-induced alterations of vascular permeability.
RESULTS: PDT significantly increased the recruitment of leukocytes and enhanced the leakage of FITC-D. Neutralization of adhesion molecules before PDT suppressed the rolling of leukocytes along the venular endothelium and significantly reduced the extravasation of FITC-D as compared to control animals (156 ± 27 vs. 11 ± 2 (mean ± SEM, number of WBC/30 seconds mm vessel circumference; P < 0.05) at 90 minutes after PDT and 194 ± 21 vs. 14 ± 4 at 180 minutes after PDT). In contrast, leukocyte sticking was not downregulated by the antibody treatment.
CONCLUSION: Leukocyte recruitment plays an essential role in the permeability-enhancing effect of PDT.
Keywords
Animals, Capillary Permeability/drug effects, Dextrans/pharmacokinetics, Drug Delivery Systems, Endothelial Cells/drug effects, Female, Fluorescein-5-isothiocyanate/analogs & derivatives, Fluorescein-5-isothiocyanate/pharmacokinetics, Fluorescent Dyes/pharmacokinetics, Leukocytes/drug effects, Mice, Mice, Nude, Microscopy, Fluorescence, Photochemotherapy, Photosensitizing Agents/pharmacology, Porphyrins/pharmacology
Pubmed
Web of science
Create date
08/11/2011 15:24
Last modification date
20/08/2019 15:57
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