Combe C, Duplàa C, Couffinhal T, Moreau C, Bonnet J
Institut National de la Santé et de la Recherche Médicale, Unité 8 de Cardiologie, Pessac, France.
J Cell Physiol. 1995 Aug;164(2):295-303. doi: 10.1002/jcp.1041640210.
Increased monocyte adhesion to the endothelial lining of blood vessels by cytokine-inducible adhesion proteins is a crucial event in inflammatory processes. Moreover, adherence is known to induce cytokine gene expression, suggesting a possible positive feedback mechanism. Therefore, we determined whether monocyte adhesion to endothelial cells (ECs) amplifies their adhesion by inducing intercellular adhesion molecule 1 (ICAM-1), and whether such positive feedback mechanism could be mediated by secretion of interleukin-1 (IL-1). Using monocyte-EC couples obtained after monocyte adhesion to ECs, and methods of quantitative polymerase chain reaction and immunofluorescence flow cytometry, we showed a biphasic increase of ICAM-1 mRNA content (2 and 16 hours) and a time-dependent increase of cell surface expression of ICAM-1, mainly on ECs, and couple adhesiveness, after monocyte adhesion to ECs. Anti-ICAM-1 monoclonal antibody inhibited 63% of the enhancement of adhesiveness induced on monocyte-EC couples by previous monocyte adhesion, suggesting that monocyte adhesion to ECs induces an increase of couple adhesiveness which is partially dependent on the ICAM-1 pathway. The early ICAM-1 mRNA induction was associated with a fast induction of IL-1 beta mRNA and a 7.7-fold increase in IL-1 beta protein in supernatant. However, 30% of this 2-hour ICAM-1 mRNA peak was abolished by recombinant soluble human IL-1 receptor, suggesting that the early ICAM-1 over-expression was partially mediated by IL-1 beta, and could be induced directly by adherence. The second ICAM-1 mRNA peak was accompanied by a marked increase in IL-1 beta mRNA and protein secretion (2.6 ng/ml). The binding to ICAM-1 did not appear to directly stimulate IL-1 beta synthesis. These results indicate that monocyte adhesion to endothelial cells appears to stimulate their own recruitment via induction of ICAM-1 thereby constituting a self-perpetuating positive feedback system.
细胞因子诱导的黏附蛋白使单核细胞与血管内皮的黏附增加是炎症过程中的关键事件。此外，已知黏附可诱导细胞因子基因表达，提示可能存在正反馈机制。因此，我们确定单核细胞与内皮细胞（ECs）的黏附是否通过诱导细胞间黏附分子1（ICAM-1）来增强其黏附，以及这种正反馈机制是否可由白细胞介素-1（IL-1）的分泌介导。利用单核细胞黏附于ECs后获得的单核细胞-EC对，以及定量聚合酶链反应和免疫荧光流式细胞术方法，我们发现单核细胞黏附于ECs后，ICAM-1 mRNA含量呈双相增加（2小时和16小时），ICAM-1细胞表面表达呈时间依赖性增加，主要在ECs上，且对的黏附性增加。抗ICAM-1单克隆抗体抑制了先前单核细胞黏附在单核细胞-EC对上诱导的黏附性增强的63%，提示单核细胞黏附于ECs诱导对黏附性增加，这部分依赖于ICAM-1途径。早期ICAM-1 mRNA诱导与IL-1β mRNA的快速诱导以及上清液中IL-1β蛋白增加7.7倍相关。然而，重组可溶性人IL-1受体消除了这个2小时ICAM-1 mRNA峰值的30%，提示早期ICAM-1的过度表达部分由IL-1β介导，且可由黏附直接诱导。第二个ICAM-1 mRNA峰值伴随着IL-1β mRNA和蛋白分泌的显著增加（2.6 ng/ml）。与ICAM-1的结合似乎并未直接刺激IL-1β合成。这些结果表明，单核细胞黏附于内皮细胞似乎通过诱导ICAM-1来刺激其自身的募集，从而构成一个自我持续的正反馈系统。
