title: Modulation of human neutrophil activity by adenosine modified with a carborane pharmacophore.
abstract: An impact of adenosine modification with electroneutral, lipophilic 1,12-dicarba-closo-dodecaborane or electronegative 7,8-dicarba-nido-undecaborane boron cluster at the 6-N, 2'-C and 2-C positions on human neutrophil oxidative burst, neutrophil adherence to fibronectin and protein kinase C activity was studied. Modification of adenosine with 1,12-dicarba-closo-dodecaborane, but not 7,8-dicarba-nido-undecaborane, changes the function of adenosine from an inactive to an active state in regulating neutrophil response to PMA stimulation by reducing neutrophils' reactivity through a mechanism involving the PKC signaling pathway. Our results show that exogenously administered adenosine derivatives can be useful in regulating the oxidative burst of neutrophils in the inflammatory process.
authors.affiliation: Laboratory of Experimental Immunology, Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa St., 93-232 Lodz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bednarska
authors.affiliation: Screening Laboratory, Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa St., 93-232 Lodz, Poland.
authors.forename: Agnieszka B
authors.initials: AB
authors.lastname: Olejniczak
authors.affiliation: Laboratory of Experimental Immunology, Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa St., 93-232 Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Klink
authors.affiliation: Laboratory of Experimental Immunology, Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa St., 93-232 Lodz, Poland.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Sułowska
authors.affiliation: Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa St., 93-232 Lodz, Poland. Electronic address: zlesnikowski@cbm.pan.pl.
authors.forename: Zbigniew J
authors.initials: ZJ
authors.lastname: Leśnikowski
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D001881:Borates / Q000737:chemistry*; D001896:Boron Compounds / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C535189:7,8-dicarba-nido-undekaborate; D001881:Borates; D001896:Boron Compounds; D000241:Adenosine
keywords: Carborane conjugates; Neutrophils; Nucleosides; Oxidative burst; Reactive oxygen species (ROS)