Sulfated vizantin induces formation of macrophage extracellular traps

Abstract

Vizantin is an insoluble adjuvant that activates macrophages and lymphocytes. Recently, 2,2',3,3',4,4'-hexasulfated-vizantin (sulfated vizantin), which enables solubilization of vizantin, was developed by the present team. Sulfated vizantin was found to enhance bactericidal activity against multi-drug resistant Pseudomonas aeruginosa in RAW264.7 cells. In addition, spread of P. aeruginosa was inhibited in RAW264.7 cells treated with sulfated vizantin. When only sulfated vizantin and P. aeruginosa were incubated, sulfated vizantin did not affect growth of P. aeruginosa. Formation of DNA-based extracellular traps (ETs), a novel defense mechanism in several types of innate immune cells, helps to eliminate pathogens. In the present study, ET-forming macrophages constituted the majority of immune cells. Sulfated vizantin induced ET formation in RAW264.7 cells, whereas a Ca-chelating reagent, EDTA, and T-type calcium channel blocker, tetrandrine, inhibited ET formation and attenuated inhibition of spread of P. aeruginosa in sulfated vizantin-treated cells. Thus, sulfated vizantin induces ET formation in phagocytic cells in a Ca-dependent manner, thus preventing spread of P. aeruginosa. Hence, sulfated vizantin may be useful in the management of infectious diseases.

Extracellular traps in kidney disease

“…The vast majority of data relate to NETs, but several reports document that ETs also are released from other immune cells including macrophages, basophils, eosinophils, and mast cells. 4,[52][53][54][55][56][57] Since the discovery of ETs, 3 it has been documented that many leukocyte activity-related tissue pathologies are at least in part ET dependent. 4,5 NET release from neutrophils may or may not involve neutrophil death, because some stimuli trigger NET release, leaving the neutrophil with an intact cell membrane and residual phagocytic functions.…”

Sulfated vizantin suppresses mucin layer penetration dependent on the flagella motility of Pseudomonas aeruginosa PAO1

“…aeruginosa wild-type PAO1 [ 14 ] and Δ fliC [ 8 ] were from our laboratory stock strains that were grown on Luria-Bertani (LB) agar plates (Nippon Becton Dickinson Company, Tokyo, Japan) or in LB broth (Nippon Becton Dickinson Company) at 37°C. Vizantin and sulfated vizantin were prepared according to previously reported procedure for their synthesis [ 29 ].…”

“…This sulfated vizantin induces DNA-based extracellular traps in phagocytic cells and induces phagocytosis of P . aeruginosa [ 29 ]; however, the mechanism associated with this activity, which directly acts on bacteria, remains unclear. In this study, we examined whether sulfated vizantin significantly inhibits P .…”

Sulfated vizantin causes detachment of biofilms composed mainly of the genus Streptococcus without affecting bacterial growth and viability

“…Viz-S was prepared as described in a previous report [39]. HGECs (Ca9-22; RIKEN BioResource Center, Ibaraki, Japan) and HGFs (ATCC PCS-201-018; Summit Pharmaceuticals International, Tokyo, Japan) were grown to 90% confluence in minimum essential medium (MEM; Life Technologies, Grand Island, NY, USA) or Dulbecco's modified Eagle's medium (DMEM; Wako Pure Chemical Industries, Osaka, Japan) containing 10% fetal bovine serum (FBS) (Japan Bio Serum, Hiroshima, Japan) and 1% penicillin-streptomycin (Wako Pure Chemical Industries) at 37°C in 5% CO 2 .…”