Deaggregators inhibit TNF-α-induced leukocyte adhesion in vitro by breaking up hydrophobic lipophilic interactions
Abstract
Hui YANG1, *, Jian CHEN2, Zheng-wu SHEN3, Xiu-jia ZHOU3, Guo-zhen JI2, *
1Department of Pediatric Gastroenterology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing 210008, China; 2Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai 200032, China; 3Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
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-α-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 neutrophils 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.
Keywords: deaggregator; hydrophobic lipophilic interaction; arteriosclerosis; TNF-α; leukocyte adhesion; neutrophil; monocytes; endothelial cell; smooth muscle cells
The authors acknowledge funding from the National Natural Science Foundation of China (No 20272078) and the Shanghai Municipal Science and Technology Commission (No 03J.C.14083).
* To whom correspondence should be addressed.
E-mail xinghui7325@sina.com (Hui YANG); jigz@mail.sioc.ac.cn (Guo-zhen JI)
Received 2014-01-15 Accepted 2014-03-21
Keywords:
1Department of Pediatric Gastroenterology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing 210008, China; 2Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai 200032, China; 3Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
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-α-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 neutrophils 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.
Keywords: deaggregator; hydrophobic lipophilic interaction; arteriosclerosis; TNF-α; leukocyte adhesion; neutrophil; monocytes; endothelial cell; smooth muscle cells
The authors acknowledge funding from the National Natural Science Foundation of China (No 20272078) and the Shanghai Municipal Science and Technology Commission (No 03J.C.14083).
* To whom correspondence should be addressed.
E-mail xinghui7325@sina.com (Hui YANG); jigz@mail.sioc.ac.cn (Guo-zhen JI)
Received 2014-01-15 Accepted 2014-03-21