title: Human neutrophils synthesize IL-8 in an IgE-mediated activation.
abstract: It has been demonstrated that neutrophils are responsible for the release of large amounts of the inflammatory chemokine interleukin-8 (IL-8), associated with inflammation. To further define the mechanisms implicated, we have analyzed the response of human neutrophils from allergic patients to specific antigens or challenge with anti-immunoglobulin (Ig)E antibodies. Neutrophils showed a dose- and time-dependent production of IL-8. The release of the cytokine was parallel to expression of IL-8 mRNA analyzed by the polymerase chain reaction. This expression was transient-it occurred after 3 h of anti-IgE treatment and was maintained for 18 h. Trifluoperazine, EGTA, reduced nicotinamide adenine dinucleotide phosphate-oxidase inhibitors, and reactive oxygen species (ROS) scavengers inhibited IL-8 production, indicating a critical dependence of calcium and oxidative stress. Moreover, an inhibitory effect of cyclosporin A, an immunosuppressor that inhibits calcineurin activity, on IL-8 release and IL-8 mRNA expression was observed. This is the first evidence of the involvement of ROS and calcium/calcineurin in IgE-dependent IL-8 production. These findings open new perspectives into the functional role of neutrophils in IgE-associated diseases.
authors.affiliation: Departamento de Medicina, Servicio de Immunología y alergia, Hospital Universitario Virgen Macarena, Sevilla, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Monteseirín
authors.forename: Pedro
authors.initials: P
authors.lastname: Chacón
authors.forename: Antonio
authors.initials: A
authors.lastname: Vega
authors.forename: Rajaa
authors.initials: R
authors.lastname: El Bekay
authors.forename: Moisés
authors.initials: M
authors.lastname: Alvarez
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Alba
authors.forename: Manuel
authors.initials: M
authors.lastname: Conde
authors.forename: Juan
authors.initials: J
authors.lastname: Jiménez
authors.forename: Juan A
authors.initials: JA
authors.lastname: Asturias
authors.forename: Alberto
authors.initials: A
authors.lastname: Martínez
authors.forename: José
authors.initials: J
authors.lastname: Conde
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pintado
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Bedoya
authors.forename: Francisco
authors.initials: F
authors.lastname: Sobrino
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology* / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D009249:NADP / Q000037:antagonists & inhibitors / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects / Q000276:immunology
chemical_list: D000906:Antibodies; D065095:Calcineurin Inhibitors; D016166:Free Radical Scavengers; D007166:Immunosuppressive Agents; D016209:Interleukin-8; D012333:RNA, Messenger; D007073:Immunoglobulin E; D009249:NADP; D019703:Calcineurin; D002118:Calcium