Riaz Amjid Ali, Wan Ming Xiu, Schaefer Thilo, Schramm Rene, Ekberg Henrik, Menger Michael D, Jeppsson Bengt, Thorlacius Henrik
Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
Ann Surg. 2002 Dec;236(6):777-84; discussion 784. doi: 10.1097/00000658-200212000-00010.
To study the adhesive mechanisms underlying ischemia/reperfusion (I/R)-induced leukocyte-endothelium interactions in the colon.
Leukocyte recruitment is a key feature in I/R-induced tissue injury, but the mechanisms regulating leukocyte rolling and adhesion in the colon are not known. The authors recently developed a new model to study the molecular mechanisms of I/R-provoked leukocyte-endothelium interactions in the colon microcirculation using inverted intravital fluorescence microscopy.
The superior mesenteric artery was occluded for 30 minutes and leukocyte responses were analyzed after 120 minutes of reperfusion in colonic venules in mice. The adhesive mechanisms underlying I/R-induced leukocyte rolling and adhesion were investigated using monoclonal antibodies against L-, E- and P-selectin, and CD11a gene-targeted mice were used to examine the role of lymphocyte function antigen-1 (LFA-1, CD11a/CD18).
Reperfusion provoked a clear-cut increase in leukocyte rolling and adhesion in colonic venules compared to negative controls. Both P- and E-selectin mRNA were expressed in the colon after this I/R insult. Pretreatment with an anti-P-selectin antibody reduced leukocyte rolling and adhesion by 88% and 85%, respectively, whereas antibodies against L- and E-selectin had no effect. Moreover, I/R-induced leukocyte adhesion in LFA-1-deficient mice was reduced by more than 95%.
This study provides evidence that leukocyte rolling is exclusively and nonredundantly mediated by P-selectin and that firm adhesion is supported by LFA-1 in I/R-induced leukocyte recruitment in the colon. Taken together, both P-selectin and LFA-1 may be important targets to control pathologic inflammation in I/R-induced tissue injury in the colon.
研究结肠中缺血/再灌注（I/R）诱导的白细胞与内皮细胞相互作用的粘附机制。
白细胞募集是I/R诱导的组织损伤的关键特征，但调节结肠中白细胞滚动和粘附的机制尚不清楚。作者最近开发了一种新模型，利用倒置活体荧光显微镜研究I/R引发的结肠微循环中白细胞与内皮细胞相互作用的分子机制。
在小鼠结肠小静脉中，将肠系膜上动脉阻断30分钟，并在再灌注120分钟后分析白细胞反应。使用抗L-、E-和P-选择素的单克隆抗体研究I/R诱导的白细胞滚动和粘附的粘附机制，并使用CD11a基因靶向小鼠检查淋巴细胞功能抗原-1（LFA-1，CD11a/CD18）的作用。
与阴性对照相比，再灌注导致结肠小静脉中白细胞滚动和粘附明显增加。在这种I/R损伤后，结肠中P-和E-选择素mRNA均有表达。用抗P-选择素抗体预处理分别使白细胞滚动和粘附减少88%和85% , 而抗L-和E-选择素抗体则无作用。此外，I/R诱导的LFA-1缺陷小鼠中的白细胞粘附减少了95%以上。
本研究提供的证据表明，在结肠I/R诱导的白细胞募集中，白细胞滚动仅由P-选择素介导且无冗余，而牢固粘附则由LFA-1支持。综上所述，P-选择素和LFA-1可能都是控制结肠I/R诱导的组织损伤中病理性炎症的重要靶点。
