Differential patterns of neutrophil adhesion molecules during cardiopulmonary bypass in humans.
Differential patterns of neutrophil adhesion molecules during cardiopulmonary bypass in humans.
复制标题
人类体外循环期间中性粒细胞粘附分子的差异模式。
作者：
M. Galiñanes;C. Watson;U. Trivedi;D. Chambers;C. Young;G. Venn
背景
中性粒细胞在体外循环过程中被激活，并且被认为在术后炎症反应中起重要作用。中性粒细胞的作用由表面粘附分子L-选择素、β 2-整联蛋白和血小板-内皮细胞粘附分子-1（PECAM-1）介导，并且已经报道，体外循环上调β 2-整联蛋白，下调L-选择素。然而，这些变化的时间进程及其相对重要性尚不清楚。
方法和结果
为了研究体外循环诱导的中性粒细胞表面粘附分子L-选择素、β 2-整合素和PECAM-1表达的时间变化，我们使用免疫荧光流式细胞术检测了不同时间获得的血液样本（麻醉前、搭桥术前和搭桥术开始后0.25、0.5、1、2、4、24和48小时）。麻醉对任何研究分子的表达没有影响。在整个研究期间，所有β 2-整合素的表达均未受到显著影响。在心肺转流开始后的前2小时内，CD 18的平均荧光（表示为对照的百分比）没有显著变化，但随后在4小时内下降（P = NS），并在24和48小时后达到最低值。CD 11b和CD 11 c的平均荧光在2小时和4小时降低，并在24小时和48小时后保持降低。PECAM-I的表达在体外循环开始后迅速下降，达到麻醉前对照值的60 ± 8%（P < .05），4小时后降至最低（44 +/- 8%; P <0.05）;然后在24小时部分恢复（60 +/- 11%; P <0.05），48小时后进一步恢复至对照组（77 +/- 8%; P = NS）。PECAM-I的平均荧光谱与其表达所观察到的相同。与此相反，L-选择素的表达和平均荧光在48小时内没有变化。
结论
这项研究表明，人体心肺转流术诱导（1）循环中性粒细胞PECAM-1表达的快速降低，（2）β 2-整合素活性的后期降低，而其表达无显著变化，（3）L-选择素的表达和活性无改变。因此，尽管中性粒细胞β 2-整联蛋白上调和L-选择素下调（无活化）的机制尚待阐明，但PECAM-1的下调表明早期中性粒细胞活化，其抑制可能代表减少通常与心肺转流相关的炎症反应的靶点。
BACKGROUND
Neutrophils are activated during cardiopulmonary bypass, and it is believed that they play an important role in the postoperative inflammatory response. The effects of neutrophils are mediated by the surface adhesion molecules L-selectin, beta 2-integrins, and platelet-endothelial cell adhesion molecule-1 (PECAM-1), and it has been reported that beta 2-integrins are upregulated and L-selectin downregulated by cardiopulmonary bypass. However, the time course of these changes and their relative importance are unclear.
METHODS AND RESULTS
To investigate the temporal changes in the expression of the neutrophil surface adhesion molecules L-selectin, beta 2-integrins, and PECAM-1 induced by cardiopulmonary bypass, we used immunofluorescent flow cytometry in blood samples obtained at various times (before anesthesia, before bypass, and 0.25, 0.5, 1, 2, 4, 24, and 48 hours after initiation of bypass) from patients undergoing routine coronary artery bypass graft surgery. Anesthesia had no effect on the expression of any of the study molecules. The expression of all beta 2-integrins was not significantly affected during the entire study period. The mean fluorescence (expressed as a percentage of control) of CD18 did not change significantly during the first 2 hours after the initiation of cardiopulmonary bypass, but then it declined by 4 hours (P = NS) and attained its lowest values after 24 and 48 hours. The mean fluorescence of CD11b and CD11c decreased by 2 and 4 hours and remained reduced after 24 hours and 48 hours. The expression of PECAM-I decreased rapidly after the initiation of cardiopulmonary bypass to achieve 60 +/- 8% of the preanesthesia control values (P < .05) after only 1 hour; it fell to its lowest after 4 hours (44 +/- 8%; P < .05); and then it recovered partially by 24 hours (60 +/- 11%; P < .05), with a further recovery toward control after 48 hours (77 +/- 8%; P = NS). The profile for the mean fluorescence of PECAM-I was identical to that observed with its expression. In contrast, the expression and mean fluorescence of L-selectin were not changed during the 48-hour period.
CONCLUSIONS
This study has demonstrated that cardiopulmonary bypass in humans induces (1) a rapid reduction in the expression of PECAM-I of circulating neutrophils, (2) a later reduction of beta 2-intergrin activity without significant changes in their expression, and (3) no alterations in the expression and activity of L-selectin. Thus, although the mechanism for the absence of neutrophil upregulation of beta 2-integrins and downregulation of L-selectin (no activation) remains to be elucidated, the downregulation of PECAM-1 indicates an early neutrophil activation, and its inhibition may represent a target for reducing the inflammatory response usually associated with cardiopulmonary bypass.