title: Leukocyte-endothelial cell interaction is necessary for photodynamic therapy induced vascular permeabilization.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  Leukocyte recruitment plays an essential role in the permeability-enhancing effect of PDT.
authors: Department of Thoracic and Vascular Surgery, CHUV Hospital, Faculty of Biology and Medicine, University of Lausanne, CH-1011 Lausanne, Switzerland.
authors: Elodie
authors: E
authors: Debefve
authors: François
authors: F
authors: Mithieux
authors: Jean Y
authors: JY
authors: Perentes
authors: Yabo
authors: Y
authors: Wang
authors: Cai
authors: C
authors: Cheng
authors: Stephan C
authors: SC
authors: Schaefer
authors: Christiane
authors: C
authors: Ruffieux
authors: Jean-Pierre
authors: JP
authors: Ballini
authors: Michel
authors: M
authors: Gonzalez
authors: Hubert
authors: H
authors: van den Bergh
authors: Hans-Beat
authors: HB
authors: Ris
authors: Hans-Anton
authors: HA
authors: Lehr
authors: Thorsten
authors: T
authors: Krueger
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D003911:Dextrans / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000187:drug effects*; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D007962:Leukocytes / Q000187:drug effects*; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D000077362:Verteporfin
chemical_list: D003911:Dextrans; D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D011166:Porphyrins; C015219:fluorescein isothiocyanate dextran; D000077362:Verteporfin; D016650:Fluorescein-5-isothiocyanate