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Eosinophil Trans-Basement Membrane Migration Induced by Interleukin-8 and Neutrophils

Department of Respiratory Medicine, Saitama Medical School, Saitama, Japan; and Department of Allergy and Respiratory Medicine, Kanto Central Hospital of the Mutual Aid Association of Public School Teachers, Tokyo, Japan

Correspondence and requests for reprints should be addressed to Makoto Nagata M.D., Ph.D., Department of Respiratory Medicine, Saitama Medical School, Saitama, Japan. E-mail: favre4mn{at}saitama-med.ac.jp

Neutrophilic inflammation observed with severe asthma is often associated with interleukin-8 (IL-8). Neutrophils can secrete a variety of mediators that may augment the migration of eosinophils. We have reported a positive correlation between the concentrations of neutrophils and eosinophils in sputum from subjects with severe asthma, suggesting a possible role of neutrophils in regulating eosinophilic inflammation. The aim of this study was to investigate whether neutrophils stimulated with IL-8 modify the trans-basement membrane migration (TBM) of eosinophils. Eosinophils and neutrophils were isolated from peripheral blood drawn from healthy donors or subjects with mild asthma. The TBM of eosinophils in response to IL-8 was evaluated in the presence or absence of neutrophils using the chambers with a Matrigel-coated transwell insert. Neither IL-8 alone nor the presence of neutrophils alone induced the TBM of eosinophils. However, when eosinophils were coincubated with neutrophils and stimulated with IL-8, the TBM of eosinophils was significantly augmented. This augmented TBM of eosinophils was inhibited by a matrix metalloproteinase-9 inhibitor, a leukotriene B₄ receptor antagonist, platelet-activating factor antagonists, or an anti–TNF- monoclonal antibodies. These results suggest that neutrophils migrated in response to IL-8 may lead eosinophils to accumulate in the airways of asthma and possibly aggravate this disease.

Key Words: eosinophils • growth-related oncogene- • interleukin-8 • neutrophils • trans-basement membrane migration

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