Friday, October 31, 2008
14665

Upregulation of leukocyte cell adhesion molecules in radiated tissues

Martin Halle, MD, Filip Farnebo, MD, PhD, and Per Tornvall, MD, PhD.

Introduction
Surgical wounds within previously irradiated tissues are subject to an increased incidence of postoperative complications including microvascular occlusion and impaired wound healing. The high radiation sensitivity of the vasculature has previously mainly been linked to endothelial dysfunction. However, the vascular biology behind the tissue damage is mot fully understood. In the present study, we have studied the gene expression of leukocyte adhesion molecules after irradiation.
Material and Methods
Radiated cervical neck arteries were harvested during head and neck cancer resection in 13 preoperativelly radiated patients and analyzed together with 13 nonradiated controls. The age of the radiated  patients ranged from 46 to 68 years with a mean of 56.9 years in 11 patients. In these patients, total preoperative dose of radiation averaged 60.4 Gy with a range of 50-68 Gy whereas the time elapsed from termination of radiotherapy to harvest of biopsy ranged from 4 to 500 weeks with a median of 6.5 weeks. Age, dose and time-point for radiation were unknown for two of the radiated patients. RT-PCR was used to investigate gene expression of leukocyte adhesion molecules.
Results
The results obtained showed a significant upregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin (SELE) in the radiated arteries compared to controls. There was an increase in upregulation between week 4 to 7, with a gradual decrease at later time points for both ICAM-1 and SELE, whereas a susitained high level was seen for VCAM-1
Conclusion
We conclude that there is a significant upregulation of  ICAM-1, V-CAM and SELE in radiated tissues. It is known that the increased adhesion of leukocytes to endothelium can impair microcirculation and promote thrombosis. We therefor believe that the upregulation of adhesion molecules  play an important role in the development of impaired vascular function and tissue damage in radiated tissues.