Human neutrophils synthesize IL-8 in an IgE-mediated activation.
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.
Monteseirín
Javier
J
Departamento de Medicina, Servicio de Immunología y alergia, Hospital Universitario Virgen Macarena, Sevilla, Spain.
Chacón
Pedro
P
Vega
Antonio
A
El Bekay
Rajaa
R
Alvarez
Moisés
M
Alba
Gonzalo
G
Conde
Manuel
M
Jiménez
Juan
J
Asturias
Juan A
JA
Martínez
Alberto
A
Conde
José
J
Pintado
Elizabeth
E
Bedoya
Francisco J
FJ
Sobrino
Francisco
F
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
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