Irradiation induces increase of adhesion molecules and accumulation of beta2-integrin-expressing cells in humans

Int J Radiat Oncol Biol Phys. 1999 Sep 1;45(2):475-81. doi: 10.1016/s0360-3016(99)00202-3.

Abstract

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 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.

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, 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.

MeSH terms

  • Aged
  • Cell Adhesion Molecules / metabolism
  • Cell Adhesion Molecules / radiation effects*
  • Dose-Response Relationship, Radiation
  • E-Selectin / metabolism
  • E-Selectin / radiation effects
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Integrin alpha4beta1
  • Integrins / metabolism
  • Integrins / radiation effects
  • Intercellular Adhesion Molecule-1 / metabolism
  • Intercellular Adhesion Molecule-1 / radiation effects
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Lymphocyte Function-Associated Antigen-1 / radiation effects
  • Macrophage-1 Antigen / metabolism
  • Macrophage-1 Antigen / radiation effects
  • Middle Aged
  • Mouth Mucosa / metabolism
  • Mouth Mucosa / pathology
  • Mouth Mucosa / radiation effects
  • Prospective Studies
  • Radiation Injuries / metabolism*
  • Radiation Injuries / pathology
  • Receptors, Lymphocyte Homing / metabolism
  • Receptors, Lymphocyte Homing / radiation effects
  • Stomatitis / etiology
  • Stomatitis / metabolism*
  • Stomatitis / pathology
  • Time Factors
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Vascular Cell Adhesion Molecule-1 / radiation effects

Substances

  • Cell Adhesion Molecules
  • E-Selectin
  • Integrin alpha4beta1
  • Integrins
  • Lymphocyte Function-Associated Antigen-1
  • Macrophage-1 Antigen
  • Receptors, Lymphocyte Homing
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1