Molecules involved in the adhesion and cytotoxicity of activated monocytes on endothelial cells.
Molecules involved in the adhesion and cytotoxicity of activated monocytes on endothelial cells.
复制标题
参与活化单核细胞在内皮细胞上的粘附和细胞毒性的分子。
作者：
N. Jonjić;P. Jílek;S. Bernasconi;G. Peri;I. Martìn‐padura;S. Cenzuales;E. Dejana;A. Mantovani
我们的研究旨在探讨活化的人单核细胞对静止和il -1刺激的内皮细胞（EC）的粘附和细胞毒性的表面分子。单核细胞暴露于ifn - γ和LPS的原型激活刺激下，与静止和il -1处理的EC结合增加。在24- 48小时[3H]TdR释放试验中，激活的单核细胞对静息和il -1处理的EC具有细胞毒性。Anti-CD18 mAb显著抑制单核细胞与EC的结合：特别是它们分别使激活的单核细胞对静止和il -1刺激的EC的粘附抑制了59%和22%。抗vla4单抗单独使用时对结合几乎没有影响，但与抗cd18联合使用揭示了这种粘附途径的重要作用：特别是，vla4依赖性粘附占激活单核细胞与il -1处理的EC结合的40%。Anti-CD18 mAb对静止和il -1处理的EC的活化单核细胞的细胞毒性有相似的抑制作用（77%和81%），尽管该途径仅占与活化EC结合的22%。此外，抗vla4单抗单独使用或与抗cd18联合使用对细胞毒性没有影响。这些结果表明，活化单核细胞与活化EC的粘附涉及CD18-和vla4依赖性途径，但前者在细胞毒性表达中占主导地位。因此，在内皮细胞和活化单核细胞之间相互作用的粘附分子的集合中，它们的重要性等级可能因不同的功能而异。
Our study was designed to investigate the surface molecules involved in the adhesion and cytotoxicity of activated human monocytes on resting and IL-1-stimulated endothelial cells (EC). Monocytes, exposed to the prototypic activating stimuli IFN-gamma and LPS, showed increased binding to resting and IL-1-treated EC. Activated monocytes were cytotoxic for resting and IL-1-treated EC in a 24- to 48-h [3H]TdR release assay. Anti-CD18 mAb significantly inhibited binding of monocytes on EC: in particular they caused 59 and 22% inhibition of adhesion of activated monocytes to resting and IL-1-stimulated EC, respectively. Anti-VLA4 mAb had little or no effect on binding when used alone, but combined use with anti-CD18 revealed an important role for this adhesion pathway: in particular, VLA4-dependent adhesion accounted for 40% of the binding of activated monocytes on IL-1-treated EC. Anti-CD18 mAb caused similar inhibition (77 and 81%) of the cytotoxicity of activated monocytes on resting and IL-1-treated EC in spite of the fact that this pathway accounted for only 22% of binding to activated EC. Moreover, anti-VLA4 mAb, alone or in combination with anti-CD18, had no effect on cytotoxicity. These results suggest that adhesion of activated monocytes to activated EC involves the CD18- and VLA4-dependent pathways, but that the former is dominant for the expression of cytotoxicity. Thus, in the ensemble of adhesion molecules available for interaction between endothelium and activated monocytes, the hierarchy of their importance may vary for different functions.