Möbert J, Zahler S, Becker B F, Conzen P F
Institute of Physiology, University of Munich, Germany.
Anesthesiology. 1999 May;90(5):1372-81. doi: 10.1097/00000542-199905000-00022.
Polymorphonuclear leukocytes (neutrophils, PMNs) have been shown to mediate vascular and tissue injury, leading to so-called systemic inflammatory response syndrome. The authors evaluated the effect of volatile anesthetics on neutrophil adhesion to human endothelial cells, focusing on whether the inhibitory effect observed is linked to an alteration in the function of endothelial cells or neutrophils.
The adhesion of human PMNs was quantified using cultured human umbilical vein endothelial cells (HUVECs). The increase in the number of adhering PMNs was assessed when HUVECs (with 1 mM hydrogen peroxide), PMNs (with 10 nM N-formyl-methionyl-leucyl-phenylalanine), or both were prestimulated. To determine the influence of volatile anesthetics on the adhesion of PMNs, the experiments were performed in the absence or presence of 0.5, 1, and 2 minimum alveolar concentration halothane, isoflurane, or sevoflurane, whereby HUVECs, PMNs, or both were pretreated with gas.
Activation of HUVECs with hydrogen peroxide or stimulation of PMNs with N-formyl-methionyl-leucyl-phenylalanine resulted in a 2.5-fold increase in PMN adhesion. Preincubation of PMNs, separately, with halothane, isoflurane, or sevoflurane, respectively, abolished enhanced neutrophil adhesion to hydrogen peroxide-activated HUVECs and adhesion of PMNs prestimulated with N-formyl-methionyl-leucyl-phenylalanine to unstimulated HUVECs (maximal effect at 1 minimum alveolar concentration). No decrease in adhesion was detected when only HUVECs were pretreated with volatile anesthetics. Additional exposure of HUVECs and PMNs to volatile anesthetics had no inhibitory effect on adhesion greater than that seen when only PMNs were treated. Appropriately, the volatile anesthetics abolished the upward regulation of the adhesion molecule CD11b on PMNs (as evaluated at 1 minimum alveolar concentration each), whereas 1 minimum alveolar concentration halothane failed to affect the expression of P-selectin, an adhesion molecule on endothelial cells.
This study indicates that halothane, isoflurane, and sevoflurane inhibit neutrophil adhesion to human endothelial cells at concentrations relevant to anesthesia in a static system. The effects appear to be mediated by inhibition of PMN activation; that is, by attenuating the upward regulation of neutrophil CD11b.
多形核白细胞（中性粒细胞，PMN）已被证明可介导血管和组织损伤，导致所谓的全身炎症反应综合征。作者评估了挥发性麻醉剂对中性粒细胞与人内皮细胞黏附的影响，重点关注观察到的抑制作用是否与内皮细胞或中性粒细胞功能的改变有关。
使用培养的人脐静脉内皮细胞（HUVEC）对人PMN的黏附进行定量。当HUVEC（用1 mM过氧化氢）、PMN（用10 nM N-甲酰甲硫氨酰亮氨酰苯丙氨酸）或两者均被预刺激时，评估黏附PMN数量的增加。为了确定挥发性麻醉剂对PMN黏附的影响，实验在不存在或存在0.5、1和2最低肺泡浓度的氟烷、异氟烷或七氟烷的情况下进行，其中HUVEC、PMN或两者均用气体预处理。
用过氧化氢激活HUVEC或用N-甲酰甲硫氨酰亮氨酰苯丙氨酸刺激PMN导致PMN黏附增加2.5倍。分别用氟烷、异氟烷或七氟烷对PMN进行预孵育，消除了中性粒细胞对过氧化氢激活的HUVEC的增强黏附以及用N-甲酰甲硫氨酰亮氨酰苯丙氨酸预刺激的PMN对未刺激的HUVEC的黏附（在1最低肺泡浓度时达到最大效应）。当仅用挥发性麻醉剂预处理HUVEC时，未检测到黏附减少。HUVEC和PMN额外暴露于挥发性麻醉剂对黏附的抑制作用不大于仅处理PMN时观察到的抑制作用。相应地，挥发性麻醉剂消除了PMN上黏附分子CD11b的上调（各自在1最低肺泡浓度时评估），而1最低肺泡浓度的氟烷未能影响内皮细胞上的黏附分子P-选择素的表达。
本研究表明，在静态系统中，氟烷、异氟烷和七氟烷在与麻醉相关的浓度下抑制中性粒细胞与人内皮细胞的黏附。其作用似乎是通过抑制PMN激活介导的；即通过减弱中性粒细胞CD11b的上调。
