Leukocyte-endothelial cell interaction is necessary for photodynamic therapy induced vascular permeabilization.
Détails
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Accès restreint UNIL
Etat: Public
Version: de l'auteur⸱e
Accès restreint UNIL
Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_9535E85BB1E8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Leukocyte-endothelial cell interaction is necessary for photodynamic therapy induced vascular permeabilization.
Périodique
Lasers In Surgery and Medicine
ISSN
1096-9101 (Electronic)
ISSN-L
0196-8092
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
43
Numéro
7
Pages
696-704
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish. PDF type: Original article
Publication Status: ppublish. PDF type: Original article
Résumé
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.
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.
Mots-clé
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
Création de la notice
08/11/2011 14:24
Dernière modification de la notice
20/08/2019 14:57