Published ahead of print on February 2, 2006, doi:10.1165/rcmb.2005-0303OC Am. J. Respir. Cell Mol. Biol., Volume 34, Number 6, June 2006, 760-765 A more recent version of this article appeared on June 1, 2006
Submitted on August 4, 2005 Eosinophil Trans-basement Membrane Migration Induced by Interleukin-8 and NeutrophilsIzumi Kikuchi1,1 Department of Respiratory Medicine, Saitama Medical School, Moroyama-machi, Iruma-gun, Saitama, Japan, 2 Department of Allergy and Respiratory Medicine, Kanto Central Hospital of the Mutual Aid Association of Public School Teachers, Tokyo, Japan * To whom correspondence should be addressed. 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 which may augment the migration of eosinophils. We have reported a positive correlation between the concentrations of neutrophils and eosinophils in sputum from severe asthmatics, suggesting a possible role of neutrophils in regulating eosinophilic inflammation. The aim of this study is 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 mild asthmatics. 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-tumor necrosis factor-
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mAb. 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.
