Geissler D, Gaggl S, Möst J, Greil R, Herold M, Dietrich M
Department of Internal Medicine, University Hospital of Innsbruck.
Eur J Immunol. 1990 Dec;20(12):2591-6. doi: 10.1002/eji.1830201210.
ICAM-1 is a cell surface glycoprotein which is one of the ligands for the leukocyte function-associated antigen (LFA-1). It is involved in leukocyte adhesion to endothelial cells as well as in immune functions requiring cell-cell contact. The quantitative expression of ICAM-1 in various cell types can be either induced or enhanced by treatment with cytokines, such as interferon-gamma (IFN-gamma), tumor necrosis factor (TNF)-alpha or interleukin 1 (IL 1), a phenomenon which results in the augmentation of binding to LFA-1-positive cells. In contrast, treatment with anti-ICAM-1 antibodies blocks this binding. A monoclonal antibody (mAb), termed 7F7, which recognizes an epitope on ICAM-1, was used to investigate the role of ICAM-1 in cytokine production by T lymphocytes and monocytes. Production of TNF-alpha. IFN-gamma and IL1 was significantly inhibited (p less than 0.01) by the incubation of mAb 7F7 with phytohemagglutinin-activated blood mononuclear cells (MNC) or isolated E rosette-positive T lymphocytes. The maximal level of inhibition was reached with 1 microgram/ml of purified antibody. A similar inhibition was obtained using saturating concentrations of 400 microliters/ml of mAb 7F7 hybridoma supernatant corresponding to an inhibitory activity of 1 microgram of purified mAb. In contrast, granulocyte/macrophage-colony-stimulating factor release showed a heterogeneous response over five experiments with an increase found in three experiments and a decrease in two experiments. Addition of increasing concentrations of supernatant or purified mAb to unstimulated MNC or T lymphocyte cultures had no effect on cytokine release. The observed inhibition of the production of TNF-alpha. IFN-gamma and IL 1 by antibody-mediated blockade of the ICAM-1 structure probably represents a negative circuit that serves to tune the activation of leukocytes and to avoid an overproduction of cytokines.
细胞间黏附分子-1（ICAM-1）是一种细胞表面糖蛋白，是白细胞功能相关抗原（LFA-1）的配体之一。它参与白细胞与内皮细胞的黏附以及需要细胞间接触的免疫功能。通过细胞因子如干扰素-γ（IFN-γ）、肿瘤坏死因子（TNF）-α或白细胞介素1（IL 1）处理，可诱导或增强ICAM-1在各种细胞类型中的定量表达，这种现象会导致与LFA-1阳性细胞结合的增加。相反，用抗ICAM-1抗体处理会阻断这种结合。一种名为7F7的单克隆抗体（mAb），可识别ICAM-1上的一个表位，用于研究ICAM-1在T淋巴细胞和单核细胞产生细胞因子中的作用。用mAb 7F7与植物血凝素激活的血液单核细胞（MNC）或分离的E花环阳性T淋巴细胞孵育，可显著抑制（p小于0.01）TNF-α、IFN-γ和IL1的产生。用1微克/毫升的纯化抗体可达到最大抑制水平。使用对应于1微克纯化mAb抑制活性的400微升/毫升mAb 7F7杂交瘤上清液饱和浓度也可获得类似的抑制效果。相反，粒细胞/巨噬细胞集落刺激因子释放显示在五个实验中有异质性反应，三个实验中增加，两个实验中减少。向未刺激的MNC或T淋巴细胞培养物中添加浓度不断增加的上清液或纯化mAb对细胞因子释放没有影响。通过抗体介导的ICAM-1结构阻断观察到的TNF-α、IFN-γ和IL 1产生的抑制可能代表一种负反馈回路，用于调节白细胞的激活并避免细胞因子的过度产生。
