Kvietys P R, Perry M A, Gaginella T S, Granger D N
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130.
Am J Physiol. 1990 Oct;259(4 Pt 1):G578-83. doi: 10.1152/ajpgi.1990.259.4.G578.
In vivo studies have implicated neutrophils in the gastric mucosal injury produced by intraluminal administration of ethanol. However, in vitro studies indicate that ethanol inhibits various neutrophil functions such as adherence, chemotaxis, and degranulation. The aim of the present study was to assess whether ethanol, at clinically relevant concentrations, is proinflammatory in vivo. Ethanol (0.2, 1.0, 2.0, and 4.0%) was applied to the surface of the cat mesentery, and neutrophil adherence to venules (30 microns diam) and extravasation into the interstitium were quantitated using intravital microscopy. Hemodynamic parameters were also measured (venular diameter, red blood cell velocity, and leukocyte rolling velocity) or calculated (venular blood flow and wall shear stress). In this model ethanol produced a dose-dependent increase in neutrophil adherence and extravasation. The increase in leukocyte-endothelial cell interactions could not be attributed to alterations in hemodynamic factors. Pretreatment of animals with a monoclonal antibody (MoAb IB4) directed to the neutrophil CD11/CD18 adherence complex completely prevented the ethanol-induced neutrophil adherence and extravasation. Pretreatment with a leukotriene B4 (LTB4)-receptor antagonist (SC 41930) or a platelet-activating factor (PAF)-receptor antagonist (WEB 2170) did not alter the ethanol-induced neutrophil-endothelial interactions. We conclude that ethanol is proinflammatory at concentrations which may be achieved in the mucosal interstitium during acute alcohol intoxication. The ethanol-induced leukocyte adherence and extravasation is dependent on the expression of adhesive glycoproteins. The inflammatory mediators, PAF and LTB4, do not appear to play an important role in the leukocyte-endothelial cell interactions initiated by ethanol.
体内研究表明，腔内给予乙醇所导致的胃黏膜损伤与中性粒细胞有关。然而，体外研究显示，乙醇会抑制多种中性粒细胞功能，如黏附、趋化和脱颗粒。本研究的目的是评估在临床相关浓度下，乙醇在体内是否具有促炎作用。将乙醇（0.2%、1.0%、2.0%和4.0%）应用于猫肠系膜表面，采用活体显微镜定量测定中性粒细胞对小静脉（直径30微米）的黏附以及向间质的渗出。还测量了血流动力学参数（小静脉直径、红细胞速度和白细胞滚动速度）或进行了计算（小静脉血流量和壁切应力）。在该模型中，乙醇导致中性粒细胞黏附和渗出呈剂量依赖性增加。白细胞与内皮细胞相互作用的增加并非归因于血流动力学因素的改变。用针对中性粒细胞CD11/CD18黏附复合物的单克隆抗体（MoAb IB4）对动物进行预处理，可完全阻止乙醇诱导的中性粒细胞黏附和渗出。用白三烯B4（LTB4）受体拮抗剂（SC 41930）或血小板活化因子（PAF）受体拮抗剂（WEB 2170）进行预处理，并不会改变乙醇诱导的中性粒细胞与内皮细胞的相互作用。我们得出结论，在急性酒精中毒期间黏膜间质中可能达到的浓度下，乙醇具有促炎作用。乙醇诱导的白细胞黏附和渗出依赖于黏附糖蛋白的表达。炎症介质PAF和LTB4似乎在乙醇引发的白细胞与内皮细胞相互作用中不起重要作用。
