title: The modulation of reactive oxygen species production from human polymorphonuclear cells by curdlan derivatives as dectin-1 agonists/antagonists.
abstract: Reactive oxygen species (ROS) are well known to be cytotoxic and have been implicated in the etiology of a wide array of human diseases including diabetes, neurodegenerative diseases, cancer and also influence central cellular processes such as proliferation, apoptosis, senescence etc. If in these pathological or degenerative conditions characterized by free radicals excess, reactive species are not eliminated, they can maintain destructive processes, already initiated at different cellular levels. Understanding the role of ROS as key mediators in signaling cascades may provide various opportunities for pharmacological intervention. Toll-like receptors and C-type lectin receptor class V--Dectin-1, as members of Pattern Recognition Receptors play an essential role in innate immune response against bacteria and fungi respectively, contributing to pathogens recognition, phagocytosis, ROS production and induction of pro-inflammatory cytokines secretion. Using a high performance chemiluminometric method, we studied the action of six Curdlan derivatives on the ROS production and release by activated human polymorphonuclear cells (PMNs) isolated from the peripheral blood of healthy donors. Our results demonstrated that Curdlan derivatives containing sulfopropyl groups did not activate human PMNs to release ROS. These compounds blocked Dectin-1 and were able to inhibit co-operation between Dectin-1 and TLR-2. Curdlan derivatives containing palmithoyl, carboxi-methyl and sulfopropyl groups increased ROS release by human PMNs activated at TLR-2 level. Taking into account the fact that Dectin-1 can actively collaborate with TLR-2 to modulate the subsequent adaptive immune response, we can presume that Curdlan derivatives containing sulfopropyl group or palmithoyl/carboxi-methyl/sulfopropyl groups, as possible Dectin-1 antagonists/agonists, could influence TLR-2 signaling.
authors.affiliation: National Institute of Research-Development for Microbiology and Immunology Cantacuzino, Immunomodulation Laboratory, Bucharest, Romania.
authors.forename: Maria-Mihaela
authors.initials: MM
authors.lastname: Bădulescu
authors.forename: Andreea-Roxana
authors.initials: AR
authors.lastname: Lupu
authors.forename: Lidia
authors.initials: L
authors.lastname: Cremer
authors.forename: Ana
authors.initials: A
authors.lastname: Călugăru
authors.forename: Natalia Simona
authors.initials: NS
authors.lastname: Apetrei
authors.forename: M
authors.initials: M
authors.lastname: Moscovici
authors.forename: Georgeta
authors.initials: G
authors.lastname: Mocanu
authors.forename: G
authors.initials: G
authors.lastname: Szegli
mesh_terms: D006801:Humans; D037181:Lectins, C-Type; D049449:Luminescence; D008565:Membrane Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors*; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D047071:beta-Glucans / Q000494:pharmacology*; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; D047071:beta-Glucans; D000099181:Dectin-1; C038459:curdlan