Terada L S, Repine J E, Piermattei D, Hybertson B M
Webb-Waring Institute for Biomedical Research, University of Colorado Health Sciences Center, Denver 80262, USA.
J Appl Physiol (1985). 1997 Mar;82(3):913-7. doi: 10.1152/jappl.1997.82.3.913.
The oxygen radical-producing enzyme xanthine oxidase (XO) can promote neutrophil adherence to endothelium. Recognizing that a balance often exists in inflammatory processes, we sought to determine whether XO initiates antiadherent pathways. We found that bovine pulmonary arterial endothelial cells (EC) exposed to XO released increased amounts of nitrite into the media, reflecting an increased production of nitric oxide (NO). When EC were subjected to shear stress, treatment with XO and/or the NO synthase inhibitor N omega-nitro-L-arginine (L-NNA) increased neutrophil rolling behavior and firm neutrophil adherence to EC in an additive fashion. Both rolling and adherent interactions were abolished by monoclonal antibodies directed against P-selectin. In addition, treatment of EC with XO and/or L-NNA increased both surface expression of P-selectin and release of von Willebrand factor into media. Finally, treatment of EC with the NO donor sodium nitroprusside decreased XO-mediated neutrophil rolling and adherence. We conclude that XO stimulates EC to produce NO and that NO decreases the P-selectin-dependent neutrophil adhesion initiated by XO. Such increases in endogenous NO may constitute an important negative-feedback response to the acute proadhesive effects of XO.
产生氧自由基的酶黄嘌呤氧化酶（XO）可促进中性粒细胞与内皮细胞的黏附。鉴于炎症过程中往往存在一种平衡，我们试图确定XO是否启动了抗黏附途径。我们发现，暴露于XO的牛肺动脉内皮细胞（EC）向培养基中释放的亚硝酸盐量增加，这反映出一氧化氮（NO）生成增加。当EC受到剪切应力作用时，用XO和/或一氧化氮合酶抑制剂Nω-硝基-L-精氨酸（L-NNA）处理会以累加方式增加中性粒细胞的滚动行为以及中性粒细胞与EC的牢固黏附。针对P-选择素的单克隆抗体可消除滚动和黏附相互作用。此外，用XO和/或L-NNA处理EC会增加P-选择素的表面表达以及血管性血友病因子向培养基中的释放。最后，用NO供体硝普钠处理EC可减少XO介导的中性粒细胞滚动和黏附。我们得出结论，XO刺激EC产生NO，而NO可减少XO引发的依赖P-选择素的中性粒细胞黏附。内源性NO的这种增加可能构成对XO急性促黏附作用的重要负反馈反应。
