Mayer Konstantin, Merfels Martina, Muhly-Reinholz Marion, Gokorsch Stephanie, Rosseau Simone, Lohmeyer Jürgen, Schwarzer Nicole, Krüll Matthias, Suttorp Norbert, Grimminger Friedrich, Seeger Werner
Medizinische Klinik II, Justus Liebig University, Klinikstrasse 36, D-35392 Giessen, Germany.
Am J Physiol Heart Circ Physiol. 2002 Aug;283(2):H811-8. doi: 10.1152/ajpheart.00235.2002.
Monocyte-endothelium interaction is a fundamental process in many acute and chronic inflammatory diseases. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are fish oil-derived alternative (omega-3) precursor fatty acids implicated in the suppression of inflammatory events. We investigated their influence on rolling and adhesion of monocytes to human umbilical vein endothelial cells (HUVEC) under laminar flow conditions in vitro. Exposure of HUVEC to tumor necrosis factor (TNF-alpha) strongly increased 1) surface expression of intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), and E-selectin, 2) platelet-activating factor (PAF) synthesis as assessed by thrombin challenge, and 3) rate of rolling and adhesion of monocytes. Preincubation of HUVEC with EPA or DHA markedly suppressed PAF synthesis, monocyte rolling, and adherence, whereas expression of endothelial adhesion molecules was unchanged. Also, PAF receptor antagonists markedly suppressed the adhesion rate of monocytes, and EPA or DHA revealed no additional inhibitory capacity. In contrast, arachidonic acid partially reversed the effect of the antagonist. We conclude that omega-3 fatty acids suppress rolling and adherence of monocytes on activated endothelial cells in vitro by affecting endothelial PAF generation.
单核细胞与内皮细胞的相互作用是许多急慢性炎症性疾病中的一个基本过程。二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）是源自鱼油的替代性（ω-3）前体脂肪酸，与炎症反应的抑制有关。我们在体外层流条件下研究了它们对单核细胞与人类脐静脉内皮细胞（HUVEC）滚动和黏附的影响。将HUVEC暴露于肿瘤坏死因子（TNF-α）会强烈增加：1）细胞间黏附分子（ICAM-1）、血管细胞黏附分子（VCAM-1）和E-选择素的表面表达；2）通过凝血酶刺激评估的血小板活化因子（PAF）合成；3）单核细胞的滚动和黏附率。用EPA或DHA对HUVEC进行预孵育可显著抑制PAF合成、单核细胞滚动和黏附，而内皮黏附分子的表达未改变。此外，PAF受体拮抗剂可显著抑制单核细胞的黏附率，且EPA或DHA未显示出额外的抑制能力。相反，花生四烯酸部分逆转了拮抗剂的作用。我们得出结论，ω-3脂肪酸通过影响内皮细胞PAF的生成，在体外抑制单核细胞在活化内皮细胞上的滚动和黏附。
