Huang Q, Wu M, Meininger C, Kelly K, Yuan Y
Departments of Surgery and Medical Physiology, Texas A & M University Health Science Center, Temple, Texas 76504, USA.
Am J Physiol. 1998 Oct;275(4):H1138-47. doi: 10.1152/ajpheart.1998.275.4.H1138.
Platelet-activating factor (PAF) has been implicated in the pathogenesis of ischemic heart disease, reperfusion injury, and inflammatory reactions. Although neutrophils have been shown to primarily mediate PAF-induced microvascular dysfunction, the vasoactive effect of PAF and its neutrophil-dependent mechanism have not been directly and systematically studied in coronary resistance vessels. Therefore, the aim of this study was to examine the effects of PAF on coronary arteriolar function and neutrophil dynamics using an isolated and perfused microvessel preparation. Topical application of PAF to the vessels induced a dose-dependent decrease in the diameter but an increase in the apparent permeability coefficient of albumin. Disruption of the endothelium abolished the vasomotor response to PAF, and perfusion of neutrophils significantly augmented PAF-induced changes in vasomotor tone and permeability. Furthermore, the interaction between neutrophils and the endothelium was studied in the intact perfused coronary arterioles. Under control conditions, there were no adherent neutrophils observed in the vessels at varied intraluminal flow velocities. However, administration of PAF caused neutrophil adhesion to the endothelium of coronary arterioles at low flow velocities. Western blot analysis indicated that PAF upregulated the expression of intercellular adhesion molecule-1 in cultured coronary microvascular endothelial cells. Taken together, the results suggest that 1) PAF induces vasoconstriction and hyperpermeability in coronary arterioles via an endothelium-dependent and neutrophil-mediated mechanism, and 2) PAF is able to stimulate neutrophil adhesion in coronary arterioles under a condition of low flow rate.
血小板活化因子（PAF）与缺血性心脏病、再灌注损伤及炎症反应的发病机制有关。尽管已表明中性粒细胞主要介导PAF诱导的微血管功能障碍，但PAF的血管活性作用及其依赖中性粒细胞的机制尚未在冠状动脉阻力血管中得到直接和系统的研究。因此，本研究的目的是使用分离并灌注的微血管制剂来研究PAF对冠状动脉小动脉功能和中性粒细胞动态的影响。将PAF局部应用于血管可导致直径呈剂量依赖性减小，但白蛋白的表观通透系数增加。内皮细胞的破坏消除了对PAF的血管舒缩反应，而灌注中性粒细胞显著增强了PAF诱导的血管舒缩张力和通透性变化。此外，在完整的灌注冠状动脉小动脉中研究了中性粒细胞与内皮细胞之间的相互作用。在对照条件下，在不同管腔内流速下未观察到血管中有黏附的中性粒细胞。然而，给予PAF会导致在低流速下中性粒细胞黏附于冠状动脉小动脉的内皮。蛋白质印迹分析表明，PAF上调了培养的冠状动脉微血管内皮细胞中细胞间黏附分子-1的表达。综上所述，结果表明：1）PAF通过内皮依赖性和中性粒细胞介导的机制诱导冠状动脉小动脉收缩和通透性增加；2）在低流速条件下，PAF能够刺激冠状动脉小动脉中的中性粒细胞黏附。
