Effects of photodynamic therapy on leucocyte-endothelium interaction: differences between normal and tumour tissue

Br J Cancer. 1995 Nov;72(5):1125-30. doi: 10.1038/bjc.1995.475.

Abstract

An inflammatory reaction is regularly noticed in irradiated tissues following photodynamic therapy (PDT). This observation is potentially associated with leucocyte-mediated tissue damage, which might further contribute to the tumoricidal effect of this therapy. The objective of our study was to investigate the effects of PDT on leucocyte-endothelium interaction in the microvasculature of tumours and normal tissue. Experiments were performed in the dorsal skinfold chamber preparation of Syrian golden hamsters bearing amelanotic melanoma A-Mel-3. The photosensitiser. Photofrin (5 mg kg-1 i.v.) was injected 24 h before laser irradiation (630 nm, 100 mW cm-2, 10 J cm-2 or 100 J cm-2). Post-capillary confluent venules (diameter 15-40 microns) of subcutaneous (s.c.) tissue or the amelanotic melanoma A-Mel-3 were observed by intravital microscopy before, 5, 30, 60 and 180 min after laser irradiation and recorded for off-line analysis. Before treatment, the number of adherent leucocytes in tumour vessels was only 22% of the number observed in vessels of s.c. tissue (P < 0.01). The maximum increase in adhering leucocytes was observed in post-capillary venules of s.c. tissue 1 h after PDT (P < 0.01). In contrast, enhanced leucocyte-endothelium interaction was missing in tumour vessels and in control groups. These results indicate that the tumour destruction observed after PDT is not mediated by leucocyte-endothelium interaction in the tumour. Induction of leucocyte adhesion in the PDT-treated normal tissue suggests a contribution to the peritumoral inflammatory response. Different maturational status or biochemical properties of tumour microvascular endothelium may explain the lack of leucocyte adherence upon PDT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Cricetinae
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology
  • Hematoporphyrin Derivative / therapeutic use*
  • Hematoporphyrin Photoradiation* / adverse effects
  • Inflammation
  • Lasers
  • Leukocytes / drug effects*
  • Leukocytes / physiology
  • Male
  • Melanoma / blood supply*
  • Melanoma / pathology
  • Muscle, Skeletal / blood supply*
  • Muscle, Skeletal / drug effects
  • Neoplasm Transplantation
  • Oxygen / metabolism
  • Photosensitizing Agents / therapeutic use*
  • Skin Window Technique
  • Venules / drug effects
  • Venules / ultrastructure

Substances

  • Photosensitizing Agents
  • Hematoporphyrin Derivative
  • Oxygen