Randolph G J, Furie M B
Department of Pathology, School of Medicine, State University of New York at Stony Brook, New York 11794, USA.
J Exp Med. 1996 Feb 1;183(2):451-62. doi: 10.1084/jem.183.2.451.
Little is known about how mononuclear phagocytes (MP) are cleared from sites of inflammation as inflammatory lesions resolve. In this study, the possibility that MP could be cleared from tissues by migrating across endothelium in the basal to apical direction was investigated. In an in vitro model of a blood vessel wall consisting of human umbilical vein endothelial cells (HUVEC) grown on amniotic tissue, a majority of MP that initially transmigrated into the amnion later exited by migrating back across the endothelium in the basal to apical direction. MP that egressed from these cultures adhered to the apical surface of the endothelium or were found nonadherent in the medium above the endothelium. Egression of MP continued throughout the 4-d period examined, displaying higher than first order kinetics and a t(1/2) of approximately 24 h. These kinetics were decreased by increasing the volume of medium bathing the cultures, suggesting that a soluble factor(s) regulates the rate of egression. In contrast, the kinetics were accelerated by pretreating the endothelium with IL-1. The initial phase of this increased rate of egression was inhibited by antibodies to inter- cellular adhesion molecule 1 (ICAM-1) or CD18 by 100 and 71%, respectively. Immunostaining revealed that ICAM-1 was present on the apical and basal surfaces of umbilical vein endothelium in vitro and in situ. These data demonstrate that MP can traverse endothelium in the basal to apical direction, and lend insight into the mechanisms by which this process occurs.
关于炎症消退时单核吞噬细胞（MP）如何从炎症部位清除，人们了解甚少。在本研究中，我们调查了MP通过从基底向顶端方向穿过内皮细胞而从组织中清除的可能性。在一个由生长在羊膜组织上的人脐静脉内皮细胞（HUVEC）组成的血管壁体外模型中，大多数最初迁移到羊膜的MP后来通过从基底向顶端方向再次穿过内皮细胞而离开。从这些培养物中逸出的MP附着在内皮细胞的顶端表面，或者在内皮细胞上方的培养基中呈非附着状态。在整个4天的观察期内，MP的逸出持续存在，显示出高于一级动力学的特征，半衰期约为24小时。通过增加培养物周围培养基的体积，这些动力学特征降低，这表明一种或多种可溶性因子调节逸出速率。相反，用IL-1预处理内皮细胞可加速动力学过程。这种逸出速率增加的初始阶段分别被细胞间黏附分子1（ICAM-1）或CD18的抗体抑制了100%和71%。免疫染色显示，ICAM-1在体外和原位的脐静脉内皮细胞的顶端和基底表面均有表达。这些数据表明，MP可以从基底向顶端方向穿过内皮细胞，并深入了解了这一过程发生的机制。
