Deaggregators inhibit TNF-a-induced leukocyte adhesion in vitro by breaking up hydrophobic lipophilic interactions

Aim： Deaggregators （deAgrs） are nontoxic organic molecules that possess the ability to deaggregate simple aggregates formed by hydrophobic lipophilic interactions （HLI）. Since HLI-driven organic molecule aggregates may induce leukocyte adhesion, we investigated the influence of deAgrs on TNF-a-media...

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Bibliographic Details
Published in:Acta pharmacologica Sinica 2014-07, Vol.35 (7), p.907-915
Main Authors: Yang, Hui, Chen, Jian, Shen, Zheng-wu, Zhou, Xiu-jia, Ji, Guo-zhen
Format: Article
Language:English
Subjects:
TNF-α
体外
特丁基对苯二酚
疏水
相互作用
细胞黏附
血管内皮细胞
诱导
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Summary:Aim： Deaggregators （deAgrs） are nontoxic organic molecules that possess the ability to deaggregate simple aggregates formed by hydrophobic lipophilic interactions （HLI）. Since HLI-driven organic molecule aggregates may induce leukocyte adhesion, we investigated the influence of deAgrs on TNF-a-mediated leukocyte adhesion in vitro. Methods： For adhesion studies, vascular endothelial cells or smooth muscle cells monolayers were treated with TNF-α （10 μg/L） and deAgrs for 24 h, followed by addition of monocytes or neutrophiis suspension. The non-adherent leukocytes were rinsed, and the number of attached leukocytes was measured using an ELISA plate reader. Simultaneously, fluorescence probes Np-12 and Np-Ch were used to measure the deaggregating efficiencies of these deAgrs. Results： Among the nine deAgrs tested,eight significantly reduced the cell adhesion rates with the order of efficiencies： 260〉160〉568〉ZPMOP〉R68〉640〉TB6PMOP〉CNS, but TBHQ had no effect. The deAgrs for deaggregating an aggregated probe （Np-12 or Np-Ch） exhibited a similar order of efficiencies： 260〉160〉568〉ZPMOP〉R68〉640〉TB6PMOP〉CNS〉12-AA〉11-AA〉TBHQ. Spearman correlation coefficient analyses indicated that the adherent rates of leukocytes to endothelial cells or smooth muscle cells treated with deAgrs had significantly negative correlation to their deaggregating abilities. Conclusion： DeAgrs effectively inhibit TNF-α-mediated leukocyte adhesion in vitro by breaking up hydrophobic lipophilic interactions, thus may be further tested for blocking atherogenesis.
ISSN:1671-4083
1745-7254
DOI:10.1038/aps.2014.32