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.
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.
Authors: Lin Yang; Richard M Froio; Tracey E Sciuto; Ann M Dvorak; Ronen Alon; Francis W Luscinskas Journal: Blood Date: 2005-04-05 Impact factor: 22.113
Authors: L Cominacini; U Garbin; A F Pasini; A Davoli; M Campagnola; G B Contessi; A M Pastorino; V Lo Cascio Journal: Free Radic Biol Med Date: 1997 Impact factor: 7.376