Irradiation induces increase of adhesion molecules and accumulation of beta2-integrin-expressing cells in humans.
OBJECTIVE
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
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 beta2-integrin-bearing cells (p < 0.01), whereas the percentage of beta1-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.


CONCLUSIONS
Our findings indicate that in radiation-induced oral mucositis there is no marked vascular damage until the end of radiotherapy. For recruitment of leukocytes, beta2 is more involved than beta1. Pharmaceuticals that block leukocyte adhesion to E-selectin or ICAM-1 may prevent radiation-mediated inflammation in oral mucosa.
Handschel
J
J
Department of Cranio- and Maxillofacial Surgery, University of Münster, Germany.
Prott
F J
FJ
Sunderkötter
C
C
Metze
D
D
Meyer
U
U
Joos
U
U
D000368:Aged; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D019040:E-Selectin / Q000378:metabolism / Q000528:radiation effects; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism / Q000528:radiation effects; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism / Q000528:radiation effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism / Q000528:radiation effects; D016177:Macrophage-1 Antigen / Q000378:metabolism / Q000528:radiation effects; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D011446:Prospective Studies; D011832:Radiation Injuries / Q000378:metabolism* / Q000473:pathology; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism / Q000528:radiation effects; D013280:Stomatitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism / Q000528:radiation effects
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1