Weyrich A S, Buerke M, Albertine K H, Lefer A M
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-6799.
J Leukoc Biol. 1995 Jan;57(1):45-55. doi: 10.1002/jlb.57.1.45.
The time course of endothelial P-selectin, ICAM-1, and E-selectin expression was studied in a feline model of myocardial ischemia and reperfusion. Cats were subjected to 90 min of myocardial ischemia followed by 0, 10, 20, 60, 150, or 270 min of reperfusion. At the end of reperfusion, the coronary vasculature was examined immunohistochemically to localize monoclonal antibodies (mAbs) PB1.3, RR1/1, and Cy1787 directed against P-selectin, ICAM-1, and E-selectin, respectively. Immunohistochemical localization for P-selectin, recognized by mAb PB1.3, was maximally expressed 20 min after reperfusion in 60 +/- 6% of coronary venules (P < 0.05 compared to non-reperfused controls), and covered 59 +/- 3% of the endothelial cell perimeter of immunostained coronary venules. Immunolocalization of mAb PB1.3 gradually declined at 60, 150, and 270 min of reperfusion. Immunohistochemical localization of mAb RR1/1 (anti-ICAM-1) in endothelial cells of coronary venules was observed to a modest extent in non-ischemic myocardium and at 10, 20, and 60 min of reperfusion, but was significantly increased following 150 and 270 min of reperfusion (P < 0.05 compared non-reperfused controls). At 270 min post-reperfusion, mAb RR1/1 was seen in 50 +/- 4% of coronary venules. Endothelial immunolocalization of mAb Cy1787 (anti-E-selectin) was only observed in 13 +/- 1 and 14 +/- 3% of coronary venules after 150 and 270 min of reperfusion, respectively, suggesting that pronounced expression of E-selectin does not occur within 270 min after reperfusion. These results demonstrate sequential expression of three major endothelial cell adherence molecules in situ following myocardial ischemia and reperfusion. The timing of endothelial cell expressed P-selectin and ICAM-1 could coordinate neutrophil trafficking during the early stages of reperfusion.
在猫心肌缺血再灌注模型中研究了内皮细胞P-选择素、细胞间黏附分子-1(ICAM-1)和E-选择素表达的时间进程。猫经历90分钟的心肌缺血,随后再灌注0、10、20、60、150或270分钟。再灌注结束时,通过免疫组织化学检查冠状血管系统,以定位分别针对P-选择素、ICAM-1和E-选择素的单克隆抗体(mAb)PB1.3、RR1/1和Cy1787。由mAb PB1.3识别的P-选择素的免疫组织化学定位在再灌注20分钟后在60±6%的冠状小静脉中最大程度表达(与未再灌注对照相比,P<0.05),并覆盖免疫染色冠状小静脉内皮细胞周长的59±3%。mAb PB1.3的免疫定位在再灌注60、150和270分钟时逐渐下降。在非缺血心肌以及再灌注10、20和60分钟时,在冠状小静脉内皮细胞中观察到mAb RR1/1(抗ICAM-1)的免疫组织化学定位程度适中,但在再灌注150和270分钟后显著增加(与未再灌注对照相比,P<0.05)。再灌注后270分钟时,可以在50±4%的冠状小静脉中看到mAb RR1/1。mAb Cy1787(抗E-选择素)的内皮免疫定位分别仅在再灌注150和270分钟后在13±1%和14±3%的冠状小静脉中观察到,表明再灌注后不到270分钟内不会出现E-选择素的明显表达。这些结果证明了心肌缺血再灌注后原位三种主要内皮细胞黏附分子的顺序表达。内皮细胞表达的P-选择素和ICAM-1的时间可以在再灌注早期阶段协调中性粒细胞的运输。