Mollà Meritxell, Gironella Meritxell, Miquel Rosa, Tovar Victoria, Engel Pablo, Biete Albert, Piqué Josep M, Panés Julián
Department of Gastroenterology, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
Int J Radiat Oncol Biol Phys. 2003 Sep 1;57(1):264-73. doi: 10.1016/s0360-3016(03)00523-6.
Cell adhesion molecules mediate leukocyte recruitment into the irradiated organs; modulation of this process may protect from radiation damage. Our objective was to characterize the requirement for intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in intestinal inflammatory response after abdominal irradiation.
Endothelial ICAM-1 and VCAM-1 expression was determined using radiolabeled antibodies in mice 24 h and 14 days after irradiation with 10 Gy, or sham radiation. Leukocyte-endothelial cell interactions in intestinal venules were assessed using intravital microscopy, and the function of ICAM-1 and VCAM-1 in this process by using blocking antibodies and ICAM-1(-/-) mice.
The number of adherent leukocytes significantly increased 24 h after irradiation and remained elevated at 14 days. Treatment with anti-ICAM-1 antibodies and ICAM-1 genetic deficiency significantly reduced leukocyte adhesion 24 h after irradiation. At 14 days after irradiation, both wild-type and ICAM-1(-/-) mice had an upregulation of VCAM-1, expression, and VCAM-1 immunoneutralization, but not ICAM-1 immunoneutralization, significantly reduced leukocyte adhesion. In ICAM-1(-/-) mice, regeneration of the intestinal epithelium was enhanced relative to wild-type mice.
ICAM-1 plays a key role in leukocyte recruitment at early time points after abdominal irradiation, whereas VCAM-1 is the main molecular determinant of leukocyte recruitment at late time points.
细胞黏附分子介导白细胞募集至受照射器官；调节这一过程可能预防辐射损伤。我们的目的是明确细胞间黏附分子1（ICAM-1）和血管细胞黏附分子1（VCAM-1）在腹部照射后肠道炎症反应中的作用。
用放射性标记抗体测定10 Gy照射或假照射后24小时及14天小鼠内皮ICAM-1和VCAM-1的表达。采用活体显微镜评估肠道小静脉中白细胞与内皮细胞的相互作用，并通过使用阻断抗体和ICAM-1基因敲除小鼠来研究ICAM-1和VCAM-1在此过程中的功能。
照射后24小时黏附白细胞数量显著增加，并在14天时仍维持在较高水平。抗ICAM-1抗体处理和ICAM-1基因缺陷显著降低了照射后24小时的白细胞黏附。照射后14天，野生型和ICAM-1基因敲除小鼠的VCAM-1表达均上调，VCAM-1免疫中和而非ICAM-1免疫中和显著降低白细胞黏附。与野生型小鼠相比，ICAM-1基因敲除小鼠的肠道上皮再生增强。
ICAM-1在腹部照射后的早期白细胞募集中起关键作用，而VCAM-1是晚期白细胞募集的主要分子决定因素。
