Arndt H, Palitzsch K D, Anderson D C, Rusche J, Grisham M B, Granger D N
Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport 71130, USA.
Gut. 1995 Sep;37(3):374-9. doi: 10.1136/gut.37.3.374.
Leucocyte-endothelial cell adhesion is modulated by a variety of adhesion glycoprotein expressed on the surface of leucocytes and endothelial cells. Although in vitro studies show that these adhesion molecules mediate the decrease in leucocyte rolling velocity and the increase in leucocyte adherence and emigration associated with inflammation, there are few in vivo data to support this hypothesis. The aim of this study was to assess the role of leucocyte (CD11b/CD18) and endothelial cell (P- and E-selectin) adhesion molecules in mediating the leucocyte-endothelial cell adhesion elicited in rat mesenteric venules during a model of longlasting intestinal inflammation. Indomethacin was injected 48 and 24 hours before the experiment. The mesenteric microcirculation was observed by intravital microscopy in animals treated with monoclonal antibodies (MAb) directed against either P-selectin, E-selectin, or CD11b/CD18. Leucocyte rolling velocity, and the number of adherent and emigrated leucocytes as well as vessel diameter and erythrocyte velocity were monitored in roughly 30 micron diameter postcapillary venules. Indomethacin treatment resulted in mucosal ulceration and granulocyte infiltration, and a corresponding inflammatory response in the mesentery, which was characterised by an increase in the number of adherent (eightfold) and emigrated (sixfold) leucocytes and a reduction (80%) in leucocyte rolling velocity. The indomethacin induced leucocyte-endothelial cell adhesion in mesenteric venules was significantly reduced by treatment with MAbs against either CD11b/CD18 or E-selectin, but not by the P-selectin MAb. These results suggest that both leukocyte (CD11b/CD18) and endothelial cell (E-selectin) adhesion molecules contribute to the granulocyte accumulation in a chronic model of intestinal inflammation.
白细胞与内皮细胞的黏附受到白细胞和内皮细胞表面表达的多种黏附糖蛋白的调节。尽管体外研究表明这些黏附分子介导了与炎症相关的白细胞滚动速度降低、白细胞黏附和迁移增加，但体内支持这一假说的数据很少。本研究的目的是评估白细胞（CD11b/CD18）和内皮细胞（P-选择素和E-选择素）黏附分子在介导大鼠肠系膜小静脉在长期肠道炎症模型中引发的白细胞与内皮细胞黏附中的作用。在实验前48小时和24小时注射吲哚美辛。通过活体显微镜观察用针对P-选择素、E-选择素或CD11b/CD18的单克隆抗体（MAb）处理的动物的肠系膜微循环。在直径约30微米的毛细血管后微静脉中监测白细胞滚动速度、黏附和迁移的白细胞数量以及血管直径和红细胞速度。吲哚美辛处理导致黏膜溃疡和粒细胞浸润，并在肠系膜中引发相应的炎症反应，其特征是黏附（增加八倍）和迁移（增加六倍）的白细胞数量增加，白细胞滚动速度降低（80%）。用针对CD11b/CD18或E-选择素的MAb处理可显著降低吲哚美辛诱导的肠系膜小静脉中白细胞与内皮细胞的黏附，但用P-选择素MAb处理则无此效果。这些结果表明，白细胞（CD11b/CD18）和内皮细胞（E-选择素）黏附分子在肠道炎症慢性模型中的粒细胞积聚中均起作用。
