Role of mast cells in oxidized low-density lipoprotein-induced microvascular dysfunction
Role of mast cells in oxidized low-density lipoprotein-induced microvascular dysfunction
复制标题
DOI：
10.1152/ajpheart.1996.271.5.h1795
复制
发表时间：
1996-11-01
影响因子：
4.8
通讯作者：
Granger, DN
中科院分区：
文献类型：
--
作者：
Liao, LX;Granger, DN
先前的研究表明，用Cu 2+氧化的人低密度脂蛋白（LDL）促进大鼠肠系膜中白细胞-内皮细胞粘附、肥大细胞脱颗粒和白蛋白渗出。本研究的目的是确定是否肥大细胞脱颗粒引起的氧化低密度脂蛋白帐户伴随的微血管反应。白细胞滚动，粘附，和移民，异硫氰酸荧光素-白蛋白泄漏，肥大细胞脱粒监测大鼠肠系膜之前和期间，无论是正常的低密度脂蛋白（nLDL）或铜氧化低密度脂蛋白（CuLDL）的局部动脉灌注。输注CuLDL，但不是nLDL，引起白细胞滚动，粘附和迁移，白蛋白渗漏，肥大细胞脱粒显着增加。用肥大细胞稳定剂酮替芬预处理或用洛度沙胺灌流肠系膜微循环显著降低CuLDL诱导的肥大细胞脱颗粒。肥大细胞的稳定伴随着减弱的白细胞-内皮细胞粘附和白蛋白渗漏反应CuLDL。本研究的结果表明，I）CuLDL诱导的微血管功能障碍（白蛋白渗漏）涉及肥大细胞的活化，2）肥大细胞稳定剂的保护作用可能与其在毛细血管后微静脉中钝化CuLDL诱导的白细胞-内皮细胞相互作用的能力有关。
Previous studies demonstrated that human low-density lipoprotein (LDL) oxidized with Cu2+ promotes leukocyte-endothelial cell adhesion, mast cell degranulation, and albumin extravasation in rat mesentery. The objective of this study was to determine whether the mast cell degranulation elicited by oxidized LDL accounts for the accompanying microvascular responses. Leukocyte rolling, adherence, and emigration, fluorescein isothiocyanate-albumin leakage, and mast cell degranulation were monitored in rat mesentery before and during local intra-arterial infusion of either normal LDL (nLDL) or copper-oxidized LDL (CuLDL). Infusion of CuLDL, but not nLDL, elicited significant increases in leukocyte rolling, adherence and emigration, albumin leakage, and mast cell degranulation. Pretreatment with the mast cell-stabilizing agent ketotifen or superfusion of the mesenteric microcirculation with lodoxamide significantly reduced CuLDL-induced mast cell degranulation. The mast cell stabilization was accompanied by attenuated leukocyte-endothelial cell adhesion and albumin leakage responses to CuLDL. The results of this study indicate that I) CuLDL-induced microvascular dysfunction (albumin leakage) involves the activation of mast cells, and 2) the protective action of mast cell stabilizers may be related to their ability to blunt CuLDL-induced leukocyte-endothelial cell interactions in postcapillary venules.