Leukocyte–endothelial cell interaction is necessary for photodynamic therapy induced vascular permeabilization
✍ Scribed by Elodie Debefve; François Mithieux; Jean Y Perentes; Yabo Wang; Cai Cheng; Stephan C. Schaefer; Christiane Ruffieux; Jean-Pierre Ballini; Michel Gonzalez; Hubert van den Bergh; Hans-Beat Ris; Hans-Anton Lehr; Thorsten Krueger
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 558 KB
- Volume
- 43
- Category
- Article
- ISSN
- 0196-8092
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✦ Synopsis
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 PDTinduced 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 1 800 mg/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 ¼ 5); control animals had PDT but no antibody injection (group ''PDT'', n ¼ 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 AE 27 vs. 11 AE 2 (mean AE SEM, number of WBC/30 seconds mm vessel circumference; P < 0.05) at 90 minutes after PDT and 194 AE 21 vs. 14 AE 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