title: The effect of cationic charge on release of eosinophil mediators.
abstract: BACKGROUND
  In patients with atopic diseases, cationic-charged eosinophil proteins are deposited in inflamed tissues. Although the role of cytokines in cell activation is well established, the presence of cationic-charged tissue can also be an important factor in inflammatory cell function.
  
  
  OBJECTIVE
  We sought to determine whether increased cationic charge seen in an atopic microenvironment plays a role in the activation of eosinophils.
  
  
  METHODS
  Human eosinophils were incubated with Sepharose beads coated with cationic or anionic compounds in the presence and absence of a cytokine cocktail (IL-3, IL-5, and GM-CSF) to simulate the milieu of inflammation. Eosinophil peroxidase and eosinophil-derived neurotoxin (EDN) release were compared with eosinophil morphology and expression of CD18, as determined by means of confocal microscopy.
  
  
  RESULTS
  Cytokines with positively charged beads caused greater eosinophil peroxidase release (lysine coated, 44.2 nmol/L; compound 48/80, 40.0 nmol/L; or EDN coated, 49.1 nmol/L) than cytokines alone (14.9 nmol/L). Beads coated with heparin, dextran sulfate, and aspartic acid did not show this effect. EDN release was also induced by lysine-coated beads with cytokines (67.1 ng/100 microL) and blocked by heparin. Eosinophil incubation with wortmannin, genistein, and the src kinase inhibitor PP1 blocked cationic signaling. Eosinophils adherent to cationic-charged beads but not anionic-charged beads show polarization of CD18 expression toward the bead's surface.
  
  
  CONCLUSIONS
  Cationic-charged surfaces induce increased eosinophil mediator release by increasing the density of CD18 expression available at the target surface.
authors.affiliation: Department of Pediatrics, Pulmonary Research Group, University of Alberta, Edmonton, Alberta, Canada. dadamko@ualberta.ca
authors.forename: Darryl J
authors.initials: DJ
authors.lastname: Adamko
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Wu
authors.forename: Farnam
authors.initials: F
authors.lastname: Ajamian
authors.forename: Ramses
authors.initials: R
authors.lastname: Ilarraza
authors.forename: Redwan
authors.initials: R
authors.lastname: Moqbel
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Gleich
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D018821:CD18 Antigens / Q000378:metabolism*; D002412:Cations; D002448:Cell Adhesion; D015550:Cell Degranulation; D016764:Cell Polarity; D016207:Cytokines / Q000276:immunology*; D016264:Dextran Sulfate / Q000494:pharmacology; D047150:Eosinophil Cationic Protein / Q000378:metabolism; D047209:Eosinophil Peroxidase / Q000378:metabolism*; D047208:Eosinophil-Derived Neurotoxin / Q000378:metabolism*; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D018821:CD18 Antigens; D002412:Cations; D016207:Cytokines; D047428:Protein Kinase Inhibitors; D017476:Receptors, Neuropeptide Y; D013267:Stilbenes; C109491:neuropeptide Y4 receptor; C041525:3,3',4,5'-tetrahydroxystilbene; D006493:Heparin; D016264:Dextran Sulfate; D019833:Genistein; D047209:Eosinophil Peroxidase; D011494:Protein Kinases; D047208:Eosinophil-Derived Neurotoxin; D047150:Eosinophil Cationic Protein; D000077191:Wortmannin