Irradiation induces increase of adhesion molecules and accumulation of β2-integrin-expressing cells in humans

Purpose: The purpose of our investigation was to describe the dose- and time-dependent histomorphologic alterations of the irradiated tissue, the composition of the infiltrate, and the expression patterns of various adhesion molecules. Methods and Materials: We analyzed immunohistochemically alterations in oral mucosa in 13 head and neck cancer patients before radiotherapy and with 30 Gy and 60 Gy. All had oral mucosa irradiation, with a final dose of 60 Gy using conventional fractionation. Snap-frozen specimens were stained using the indirect immunperoxidase technique. Histomorphology was studied in paraffin-embedded sections. In addition, we determined the clinical degree of oral mucositis. Results: Histomorphologic evaluation showed no vascular damage. Irradiation caused a steep increase of beta(2)-integrin-bearing cells (p < 0.01), whereas the percentage of beta(1)-integrin-positive cells remained at low levels. Additionally we found an increase in the expression of endothelial intercellular adhesion molecule-1 (ICAM-1) (p < 0.01) and E-selectin (p < 0.05), while endothelial vascular cell adhesion molecule-1 (VCAM-1) expression remained at very low levels. Conclusion: Our findings indicate that in radiation-induced oral mucositis there is no marked vascular damage until the end of radiotherapy. For recruitment of leukocytes, beta(2) is more involved than beta(1). Pharmaceuticals that block leukocyte adhesion to E-selectin or ICAM-1 may prevent radiation-mediated inflammation in oral mucosa, (C) 1999 Elsevier Science Inc.