Palazzo A J, Jones S P, Girod W G, Anderson D C, Granger D N, Lefer D J
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, Louisiana 71130-3392, USA.
Am J Physiol. 1998 Dec;275(6):H2300-7. doi: 10.1152/ajpheart.1998.275.6.H2300.
Previous studies have demonstrated that circulating neutrophils (PMNs) contribute to the pathophysiology of myocardial ischemia-reperfusion (MI/R) injury. PMN-endothelial cell interactions are highly regulated by adhesive interactions between PMN CD11/CD18 and coronary endothelial cell intercellular adhesion molecule-1 (ICAM-1). We investigated the effects of MI/R in wild-type, CD18-, and ICAM-1-deficient (-/-) mice. Wild-type (n = 6), CD18 -/- (n = 6), and ICAM-1 -/- (n = 6) mice were subjected to 30 min of myocardial ischemia and 120 min of reperfusion to determine the extent of PMN infiltration and myocardial cell necrosis. Myocardial infarction (% of the area at risk) was 45.1 +/- 5.9 in wild-type mouse hearts. In contrast, the extent of myocardial infarction was significantly (P < 0.05) reduced in the CD18 (19.3 +/- 5.1%)- and ICAM-1 (17.9 +/- 3.2%)-deficient mice. Similarly, PMN infiltration into the ischemic-reperfused myocardium was attenuated by 54% in the CD18 -/- mice and by 32% in ICAM-1 -/- mice compared with wild-type hearts. Deficiency in either CD18 or ICAM-1 expression results in a marked reduction in PMN accumulation and myocardial necrosis after acute MI/R.
先前的研究表明，循环中的中性粒细胞（PMN）参与了心肌缺血再灌注（MI/R）损伤的病理生理过程。PMN与内皮细胞的相互作用受到PMN CD11/CD18与冠状动脉内皮细胞细胞间黏附分子-1（ICAM-1）之间黏附相互作用的高度调控。我们研究了MI/R对野生型、CD18基因缺陷型和ICAM-1基因缺陷型（-/-）小鼠的影响。将野生型（n = 6）、CD18 -/-（n = 6）和ICAM-1 -/-（n = 6）小鼠进行30分钟的心肌缺血和120分钟的再灌注，以确定PMN浸润程度和心肌细胞坏死情况。野生型小鼠心脏的心肌梗死面积（危险区域面积的百分比）为45.1 +/- 5.9。相比之下，CD18基因缺陷型（19.3 +/- 5.1%）和ICAM-1基因缺陷型（17.9 +/- 3.2%）小鼠的心肌梗死程度显著降低（P < 0.05）。同样，与野生型心脏相比，CD18 -/-小鼠缺血再灌注心肌中的PMN浸润减少了54%，ICAM-/-小鼠减少了32%。CD18或ICAM-1表达缺陷均导致急性MI/R后PMN聚集和心肌坏死显著减少。
