Byeongtaek Oh1, Chi H Lee. 1. Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, HSB-4242, Kansas City, Missouri, 64108, USA.
Abstract
PURPOSE: The nanofiber-hydrogel blend containing nitric oxide (NO) donors and reactive oxygen species (ROS) scavengers (Edaravone: EDV) was explored as an advanced strategy for stabilization of Mast cells (MCs) to achieve efficient immune-suppressive effects. METHODS: Three types of nanofiber hydrogel composites (Bare-Nanofibers (BNF), Nanofiber-Hydrogels (NF-Gel) and Cross-linked Nanofiber-Hydrogels (NF-Gel-X)), were evaluated. The degranulation rates of MCs were determined by measurement of the extracellular levels of hydrogen peroxide and the released amounts of β-hexosaminidase from the activated-MCs (a-MCs). In addition, the effects of EDV on the selective scavenging of the oxygen radicals and prevention of peroxynitrite formation were evaluated. The roles of a-MCs in re-endothelialization and viability of coronary artery endothelial cells (hPCAECs) were defined using alamar blue and LDH assay, respectively. RESULTS: Each polymer matrix has unique morphological characteristics. The effects of EDV (~1.0 mM) on the production of NO were greatly influenced by the presence of superoxide or hydroxyl radicals. NF-G-X containing a mixture of EDV and S-Nitroglutathione (GSNO) produced the highest level of NO under the oxidative stress conditions. GSNO alone or a mixture of GSNO and EDV significantly lowered the degranulation rate of a-MCs (GSNO only: 55.8 ± 5.4%; GSNO with EDV: 50.6 ± 0.6%), indicating that NO plays an integral role in degranulation of a-MCs. There were no significant biochemical evidences of cytotoxic effects of GSNO and EDV on the hPCAECs. CONCLUSIONS: Nanofibers containing a mixture of nitric oxide donors and ROS scavengers could be used as a promising strategy to stabilize MCs from the ROS-mediated immune responses.
PURPOSE: The nanofiber-hydrogel blend containing nitric oxide (NO) donors and reactive oxygen species (ROS) scavengers (Edaravone: EDV) was explored as an advanced strategy for stabilization of Mast cells (MCs) to achieve efficient immune-suppressive effects. METHODS: Three types of nanofiber hydrogel composites (Bare-Nanofibers (BNF), Nanofiber-Hydrogels (NF-Gel) and Cross-linked Nanofiber-Hydrogels (NF-Gel-X)), were evaluated. The degranulation rates of MCs were determined by measurement of the extracellular levels of hydrogen peroxide and the released amounts of β-hexosaminidase from the activated-MCs (a-MCs). In addition, the effects of EDV on the selective scavenging of the oxygen radicals and prevention of peroxynitrite formation were evaluated. The roles of a-MCs in re-endothelialization and viability of coronary artery endothelial cells (hPCAECs) were defined using alamar blue and LDH assay, respectively. RESULTS: Each polymer matrix has unique morphological characteristics. The effects of EDV (~1.0 mM) on the production of NO were greatly influenced by the presence of superoxide or hydroxyl radicals. NF-G-X containing a mixture of EDV and S-Nitroglutathione (GSNO) produced the highest level of NO under the oxidative stress conditions. GSNO alone or a mixture of GSNO and EDV significantly lowered the degranulation rate of a-MCs (GSNO only: 55.8 ± 5.4%; GSNO with EDV: 50.6 ± 0.6%), indicating that NO plays an integral role in degranulation of a-MCs. There were no significant biochemical evidences of cytotoxic effects of GSNO and EDV on the hPCAECs. CONCLUSIONS: Nanofibers containing a mixture of nitric oxide donors and ROS scavengers could be used as a promising strategy to stabilize MCs from the ROS-mediated immune responses.
Authors: Beverley J Davis; Brian F Flanagan; Alasdair M Gilfillan; Dean D Metcalfe; John W Coleman Journal: J Immunol Date: 2004-12-01 Impact factor: 5.422