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Leukocyte–endothelial cell interaction is necessary for photodynamic therapy induced vascular permeabilization
Author(s) -
Debefve Elodie,
Mithieux François,
Perentes Jean Y,
Wang Yabo,
Cheng Cai,
Schaefer Stephan C.,
Ruffieux Christiane,
Ballini JeanPierre,
Gonzalez Michel,
van den Bergh Hubert,
Ris HansBeat,
Lehr HansAnton,
Krueger Thorsten
Publication year - 2011
Publication title -
lasers in surgery and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.888
H-Index - 112
eISSN - 1096-9101
pISSN - 0196-8092
DOI - 10.1002/lsm.21115
Subject(s) - extravasation , photodynamic therapy , intravital microscopy , vascular permeability , fluorescein isothiocyanate , in vivo , fluorescein , endothelium , pathology , chemistry , leukocyte extravasation , cell adhesion molecule , medicine , immunology , biology , fluorescence , physics , microbiology and biotechnology , quantum mechanics , organic chemistry
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/cm 2 , light dose of 200 J/cm 2 ). 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. Lasers Surg. Med. 43:696–704, 2011. © 2011 Wiley‐Liss, Inc.