Lerner R, Heimburger M, Palmblad J
Department of Medicine, Karolinska Institute, Stockholm Söder Hospital, Sweden.
Blood. 1993 Aug 1;82(3):948-53.
Lipoxin A4 (LXA4), but not lipoxin B4, induced in vitro a dose-dependent, slowly emerging hyperadhesiveness in human umbilical vein endothelial cells (HUVEC), leading to a 1.9-fold increase in the binding of neutrophils (polymorphonuclear neutrophil granulocytes [PMN]). The maximal response to LXA4 occurred at 1 nmol/L and after 30 minutes of treatment of HUVEC. These response kinetics were intermediate in comparison with those of fast-acting inducers of HUVEC adhesivity (eg, thrombin, leukotriene B4 [LTB4] or platelet activating factor [PAF]), needing 5 to 15 minutes, or to the slow inducer interleukin-1 (IL-1 beta), which requires hours. The maximal LXA4 effect was slightly lower than that of LTB4 (100 nmol/L) and thrombin (1 U/mL), and less than that of PAF (100 nmol/L) or IL-1 beta (2.5 U/mL) (2.2-, 2.0-, 2.4-, or 13.6-fold increases, respectively). The LXA4 effect was inhibited by the PAF receptor antagonist WEB-2086; however, it could not be blocked by pertussis toxin. LXA4 conferred a slow, sustained increase in HUVEC cytosolic calcium ion concentrations, whereas thrombin did so rapidly and transiently. LXA4 also caused PMN to become hyperadhesive. Thus, this novel effect of LXA4 on HUVEC appears to be associated with endogenous PAF expression and slow increases of cytosolic calcium concentrations but not pertussis-sensitive G proteins.
脂氧素A4（LXA4）而非脂氧素B4，在体外可诱导人脐静脉内皮细胞（HUVEC）产生剂量依赖性、缓慢出现的高黏附性，导致中性粒细胞（多形核中性粒细胞[PMN]）的结合增加1.9倍。对LXA4的最大反应出现在1 nmol/L，且在HUVEC处理30分钟后出现。与HUVEC黏附性的快速诱导剂（如凝血酶、白三烯B4 [LTB4]或血小板活化因子[PAF]，需5至15分钟）或缓慢诱导剂白细胞介素-1（IL-1β，需数小时）相比，这些反应动力学处于中间水平。LXA4的最大效应略低于LTB4（100 nmol/L）和凝血酶（1 U/mL），且低于PAF（100 nmol/L）或IL-1β（2.5 U/mL）（分别增加2.2倍、2.0倍、2.4倍或13.6倍）。LXA4的效应被PAF受体拮抗剂WEB-2086抑制；然而，它不能被百日咳毒素阻断。LXA4使HUVEC胞质钙离子浓度缓慢、持续增加，而凝血酶则使其迅速、短暂增加。LXA4还使PMN变得高黏附。因此，LXA4对HUVEC的这种新效应似乎与内源性PAF表达及胞质钙浓度的缓慢增加有关，而与百日咳敏感的G蛋白无关。
