Expression of ICAM-1 and acute inflammatory cell infiltration in the earlyphase of radiation colitis in rats

Inflammatory cell infiltration of the colon is observed at an early stage o f radiation-induced colitis. The emigration of inflammatory cells from the circulation requires interactions between cell adhesion molecules on the va scular 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 inflamma tory myeloperoxidase (MPO)-positive cells in relation to the appearance of acute radiation colitis prior to an overt radiation-induced ulcer. Colon ti ssues were obtained from Wistar Kyoto rats at various times after 22.5 Gy i rradiation to the rectum. Histologically, crypt depletion and numerous infl ammatory cells were observed 4 days after irradiation, and mucosal ulcer 6 days after irradiation. ICAM-1 immunopositivity was present in the endothel ial cells of small vessels in the mucosa of both control and irradiated rat s. ICAM-1 mRNA expression was detected in normal colon and irradiated colon by reverse transcription-PCR. In Northern blotting, ICAM-1 mRNA levels wer e 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 therea fter. The number of MPO-positive cells in lamina propria mucosa increased i n a rime-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.