Takahashi M, Ikeda U, Masuyama J, Kitagawa S, Kasahara T, Shimpo M, Kano S, Shimada K
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Cardiovasc Res. 1996 Aug;32(2):422-9. doi: 10.1016/0008-6363(96)00085-5.
The adhesive interaction of monocytes and endothelial cells has been implicated as a regulatory signal in the cell activation that is involved in the pathogenesis of atherosclerosis. We investigated the effect of monocyte-endothelial cell interaction on the expression of adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), in human umbilical cord vein endothelial cells (HUVECs).
ICAM-1 and VCAM-1 protein and mRNA expression were determined by cellular ELISA and Northern blot analysis, respectively.
The addition of unstimulated human monocytes, as well as interleukin-1 beta (IL-1 beta: 25 U/ml) and tumor necrosis factor-alpha (TNF: 100 U/ml), to HUVECs rapidly induced the expression of ICAM-1 and VCAM-1 protein and mRNA in HUVECs, whereas the addition of polymorphonuclear leukocytes (PMNs) had no significant effect on their expression. The induction of ICAM-1 and VCAM-1 by the co-culture of HUVECs and monocytes was significantly, but partially, inhibited by the combination of anti-IL-1 alpha, anti-IL-1 beta and anti-TNF Abs. Actinomycin D and genistein, but not calphostin C, also significantly inhibited the co-culture-induced adhesion molecule expression.
These results suggest that the monocyte-endothelial cell interaction induces the expression of ICAM-1 and VCAM-1 in endothelial cells partially through the production of IL-1 and TNF. These findings also suggest that the monocyte-endothelial interaction further augments their interaction through the up-regulation of endothelial adhesion molecules, as a positive feedback mechanism.
单核细胞与内皮细胞的黏附相互作用被认为是细胞活化中的一种调节信号，参与动脉粥样硬化的发病机制。我们研究了单核细胞 - 内皮细胞相互作用对人脐静脉内皮细胞（HUVECs）中黏附分子细胞间黏附分子 -1（ICAM -1）和血管细胞黏附分子 -1（VCAM -1）表达的影响。
分别通过细胞ELISA和Northern印迹分析测定ICAM -1和VCAM -1蛋白及mRNA表达。
向HUVECs中加入未刺激的人单核细胞以及白细胞介素 -1β（IL -1β：25 U/ml）和肿瘤坏死因子 -α（TNF：100 U/ml），可迅速诱导HUVECs中ICAM -1和VCAM -1蛋白及mRNA的表达，而加入多形核白细胞（PMNs）对其表达无显著影响。抗IL -1α、抗IL -1β和抗TNF抗体的组合可显著但部分抑制HUVECs与单核细胞共培养诱导的ICAM -1和VCAM -1表达。放线菌素D和染料木黄酮，但不是钙泊三醇，也显著抑制共培养诱导的黏附分子表达。
这些结果表明，单核细胞 - 内皮细胞相互作用部分通过IL -1和TNF的产生诱导内皮细胞中ICAM -1和VCAM -1的表达。这些发现还表明，单核细胞 - 内皮细胞相互作用通过上调内皮黏附分子进一步增强它们之间的相互作用，作为一种正反馈机制。
