Expression of ICAM-1 and Acute Inflammatory Cell Infiltration in the Early Phase of Radiation Colitis in Rats

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  • IKEDA YUJI
    Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine
  • ITO MASAHIRO
    Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine
  • MATSUU MUTSUMI
    Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine
  • SHICHIJO KAZUKO
    Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine
  • FUKUDA EIICHIRO
    Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine
  • NAKAYAMA TOSHIYUKI
    Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine
  • NAKASHIMA MASAHIRO
    Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine
  • NAITO SHINJI
    Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine
  • SEKINE ICHIRO
    Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine

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Inflammatory cell infiltration of the colon is observed at an early stage of radiation-induced colitis. The emigration of inflammatory cells from the circulation requires interactions between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. To elucidate this process, the present work analyzes the kinetics of the expression of intercellular adhesion molecule-1 (ICAM-1) and the accumulation of inflammatory myeloperoxidase (MPO)-positive cells in relation to the appearance of acute radiation colitis prior to an overt radiation-induced ulcer. Colon tissues were obtained from Wistar Kyoto rats at various times after 22.5 Gy irradiation to the rectum. Histologically, crypt depletion and numerous inflammatory cells were observed 4 days after irradiation, and mucosal ulcer 6 days after irradiation. ICAM-1 immunopositivity was present in the endothelial cells of small vessels in the mucosa of both control and irradiated rats. ICAM-1 mRNA expression was detected in normal colon and irradiated colon by reverse transcription-PCR. In Northern blotting, ICAM-1 mRNA levels were found to increase markedly in the irradiated colon compared to the normal colon. In Western blotting, ICAM-1 protein expression also increased with a peak one day after irradiation, and remained elevated up to 6 days thereafter. The number of MPO-positive cells in lamina propria mucosa increased in a time-dependent fashion from 6 h to 6 days after irradiation. These data suggest that up-regulation of ICAM-1 in endothelial cells and accumulation of MPO positive cells play important roles in the development of radiation-induced colonic ulcer.

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