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Published online before print June 3, 2004

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(Journal of Leukocyte Biology. 2004;76:692-700.)
© 2004 by Society for Leukocyte Biology

Human neutrophils synthesize IL-8 in an IgE-mediated activation

Javier Monteseirín^*,, Pedro Chacón^*, Antonio Vega^*, Rajaa El Bekay, Moisés Alvarez, Gonzalo Alba, Manuel Conde, Juan Jiménez, Juan A. Asturias, Alberto Martínez, José Conde^*, Elizabeth Pintado, Francisco J. Bedoya and Francisco Sobrino^,1

^* Departamento de Medicina, Servicio de Inmunología y Alergia, Hospital Universitario Virgen Macarena and
Clínica Sagrado Corazón, Sevilla, Spain;
Bial-Aristegui, Departamento R&D, Bilbao, Spain; and
Departamento de Bioquímica Médica y Biología Molecular, Universidad de Sevilla, Spain

¹ Correspondence: Dpto. Bioquímica Médica y Biología Molecular, Facultad de Medicina, Universidad de Sevilla, 41009-Sevilla, Spain. E-mail: fsobrino{at}us.es

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.

Key Words: anti-IgE • ROS • Ca²⁺ • calcineurin

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