Effects of photodynamic therapy on leucocyte-endothelium interaction: differences between normal and tumour tissue.
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.
Dellian
M
M
Institute for Surgical Reserch, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Abels
C
C
Kuhnle
G E
GE
Goetz
A E
AE
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D017324:Hematoporphyrin Derivative / Q000627:therapeutic use*; D006414:Hematoporphyrin Photoradiation / Q000009:adverse effects; D007249:Inflammation; D007834:Lasers; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008545:Melanoma / Q000098:blood supply* / Q000473:pathology; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000378:metabolism; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D012884:Skin Window Technique; D014699:Venules / Q000187:drug effects / Q000648:ultrastructure
D017319:Photosensitizing Agents; D017324:Hematoporphyrin Derivative; D010100:Oxygen