Klein C L, Bittinger F, Skarke C C, Wagner M, Köhler H, Walgenbach S, Kirkpatrick C J
Institute of Pathology, Johannes Gutenberg-University, Mainz, Germany.
Pathobiology. 1995;63(4):204-12. doi: 10.1159/000163953.
Cultured mesothelial cells (HOMES) are very responsive to the proinflammatory cytokines, interleukin (IL)-1 and tumor necrosis factor-alpha (TNF-alpha). E-selectin, ICAM-1 and VCAM-1 are known to play an important role, because they are presented by diverse cell types, for example endothelial cells (ECs), and interact with co-responding ligands on white blood cell membranes. In this study, the expression of ICAM-1, VCAM-1, E-selectin as well as PECAM-1 on cultured HOMES was studied over 5, 24, 48 and 72 h exposure to IL-1 beta, interferon-gamma and TNF-alpha. In previous studies we have shown that IL-1 beta and TNF-alpha increase the expression of ICAM-1, E-selectin and VCAM-1 on the cytoplasmatic membranes of HUVECs, HSVECs and HAFECs (ECs from human umbilical vein, saphenous vein and femoral artery, respectively). Using a comparative quantitative cell enzyme immunoassay, we found that expression of the adhesion molecules ICAM-1 and VCAM-1 was significantly increased on HOMES in a dose- and time-dependent manner, compared to nonstimulated cells. Thus, ICAM-1 increased dramatically after 5 h incubation with TNF-alpha. Values of about 450% of the control level were measured. VCAM-1 was similarly stimulated after 24 h incubation with the same cytokine, although its level of expression was significantly lower than that of ICAM-1. In contrast to findings in the literature, VCAM-1 was not found to be expressed constitutively. E-selectin was neither constitutively expressed nor markedly inducible on HOMES. Only weak expression was found after 24 h incubation with high-dose IL-1 beta. PECAM-1 was expressed constitutively, as became evident in antibody dilution studies. These data indicate that HOMES respond to inflammatory stimuli, in some ways in a similar fashion to vascular endothelial cells, but also show a specific pattern of antigen presentation. The results are important for a better understanding of inflammatory processes in serous cavities. The data are also relevant for the improvement of antithrombogenous surfaces of the lumina of vascular prostheses by cell seeding.
培养的间皮细胞(HOMES)对促炎细胞因子白细胞介素(IL)-1和肿瘤坏死因子-α(TNF-α)反应非常灵敏。已知E-选择素、细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)发挥重要作用,因为它们由多种细胞类型表达,如内皮细胞(ECs),并与白细胞膜上相应的配体相互作用。在本研究中,研究了培养的HOMES在暴露于IL-1β、干扰素-γ和TNF-α 5、24、48和72小时后ICAM-1、VCAM-1、E-选择素以及血小板内皮细胞黏附分子-1(PECAM-1)的表达。在先前的研究中我们已经表明,IL-1β和TNF-α会增加人脐静脉内皮细胞(HUVECs)、大隐静脉内皮细胞(HSVECs)和股动脉内皮细胞(HAFECs,分别来自人脐静脉、大隐静脉和股动脉的内皮细胞)细胞质膜上ICAM-1、E-选择素和VCAM-1的表达。使用比较定量细胞酶免疫测定法,我们发现与未刺激的细胞相比,黏附分子ICAM-1和VCAM-1在HOMES上的表达以剂量和时间依赖性方式显著增加。因此,与TNF-α孵育5小时后ICAM-1显著增加。测得的值约为对照水平的450%。与相同细胞因子孵育24小时后VCAM-1受到类似刺激,尽管其表达水平明显低于ICAM-1。与文献中的发现相反,未发现VCAM-1组成性表达。E-选择素在HOMES上既不组成性表达也不明显可诱导。与高剂量IL-1β孵育24小时后仅发现微弱表达。PECAM-1组成性表达,这在抗体稀释研究中变得明显。这些数据表明,HOMES对炎症刺激有反应,在某些方面与血管内皮细胞的反应方式相似,但也表现出特定的抗原呈递模式。这些结果对于更好地理解浆膜腔中的炎症过程很重要。这些数据对于通过细胞接种改善血管假体管腔的抗血栓形成表面也具有相关性。