Mollà M, Gironella M, Salas A, Miquel R, Pérez-del-Pulgar S, Conill C, Engel P, Biete A, Piqué J M, Panés J
Department of Gastroenterology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pí i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Int J Cancer. 2001 Apr 20;96(2):99-109. doi: 10.1002/ijc.1009.
The aims of our study were to characterize the dose- and time-dependent changes in endothelial P-selectin expression and the role of this adhesion molecule as a mediator of radiation-induced inflammation. For that purpose, endothelial P-selectin expression was measured by the radiolabeled antibody technique in control and irradiated mice at 2, 6, and 24 hr following abdominal irradiation with 4 or 10 Gy; leukocyte endothelial cell interactions were assessed using intravital microscopy in intestinal venules following irradiation at the aforementioned doses and times in C57BL/6 and P-selectin-deficient mice. In wild-type mice, radiation induced a time- and dose-dependent up-regulation of P-selectin and a significant increase in the flux of rolling leukocytes 2 hr after irradiation. Irradiation induced a significant increase in leukocyte adhesion that was dose-dependent. Following irradiation, P-selectin-deficient mice did not show any increase in leukocyte rolling but did demonstrate a response in leukocyte adhesion similar to that of the wild-type mice. Radiation-induced dose-dependent histological inflammatory damage that did not differ between P-selectin-deficient and wild-type mice. We conclude that P-selectin is up-regulated following irradiation and is a key molecular determinant of leukocyte rolling but not leukocyte adhesion in this inflammatory condition. Therefore, isolated neutralization of this adhesion molecule is not an effective means for preventing radiation-induced inflammation.
我们研究的目的是描述内皮细胞P-选择素表达的剂量和时间依赖性变化，以及这种黏附分子作为辐射诱导炎症介质的作用。为此，采用放射性标记抗体技术，在接受4或10 Gy腹部照射后2、6和24小时的对照小鼠和受照射小鼠中测量内皮细胞P-选择素的表达；在C57BL/6和P-选择素缺陷小鼠中，于上述剂量和时间照射后，使用活体显微镜评估肠小静脉中的白细胞与内皮细胞的相互作用。在野生型小鼠中，辐射诱导P-选择素呈时间和剂量依赖性上调，且照射后2小时滚动白细胞通量显著增加。辐射诱导白细胞黏附显著增加，且呈剂量依赖性。照射后，P-选择素缺陷小鼠的白细胞滚动未出现任何增加，但在白细胞黏附方面的反应与野生型小鼠相似。辐射诱导的剂量依赖性组织学炎症损伤在P-选择素缺陷小鼠和野生型小鼠之间无差异。我们得出结论，照射后P-选择素上调，是这种炎症状态下白细胞滚动而非白细胞黏附的关键分子决定因素。因此，单独中和这种黏附分子不是预防辐射诱导炎症的有效手段。
