Sulfated vizantin induces formation of macrophage extracellular traps.
Masataka OdaMie KurosawaHirofumi YamamotoHisanori DomonTatsuya KimuraToshihito IsonoTomoki MaekawaNaoki HayashiNoriteru YamadaYui FurueDaichi KaiYoshiyuki GotoPublished in: Microbiology and immunology (2018)
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.
Keyphrases
- induced apoptosis
- drug resistant
- cell cycle arrest
- pseudomonas aeruginosa
- endoplasmic reticulum stress
- immune response
- multidrug resistant
- oxidative stress
- signaling pathway
- cell death
- escherichia coli
- peripheral blood
- transcription factor
- endothelial cells
- staphylococcus aureus
- drug induced
- protein kinase
- angiotensin ii
- high glucose
- pi k akt
- gram negative