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Published online before print June 3, 2004

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0903441

Received for publication September 24, 2003.

Accepted for publication May 5, 2004.

Article

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 ^@

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

^@ To whom correspondence should be addressed. E-mail: fsobrino{at}us.es.

	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.

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

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