埼玉医科大学雑誌 第30巻 第2号別頁 (2003年4月) T11-T19頁 ◇論文(図表を含む全文)は，PDFファイルとなっています．
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医学博士 甲第862号 平成15年3月28日 （埼玉医科大学）
Effects of Neutrophils on the Trans-basement Membrane Migration and Superoxide Anion Generation of Eosinophils
Izumi Kikuchi (Pulmonary Division, Second Department of Internal Medicine, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350-0495, Japan)
Eosinophils are generally recognized as central effector cells in airway inflammation of bronchial asthma. On the other hand, neutrophils have been suggested to contribute to acute exacerbations or development of chronic severe disease of asthma. The mechanisms how neutrophils contribute to these pathophysiologic processes in asthma remains to be elucidated, however, neutrophils may affect either accumulation or functional status of eosinophils. The objective of this study was to evaluate whether the presence of neutrophils modifies trans-basement membrane migration and effector function of eosinophils. Eosinophils and neutrophils were isolated from the peripheral blood of healthy subjects. Eosinophil migration across basement membrane was evaluated using Matrigel®-coated chemotaxis chambers in the presence or absence of neutrophils. In the presence of neutrophils, trans-basement membrane migration of eosinophils in response to IL-8 was significantly augmented ( % migration; 12.9±3.1 vs. 1.9±0.5 by control, p＝0.007, N＝10). Similarly, eosinophil migration to GRO-α was also augmented in the presence of neutrophils. The enhanced migration in the presence of neutrophils was partially but significantly inhibited by PAF-antagonists, WEB2086 or WEB2170, and LTB4 receptor antagonist, BIIL260, suggesting the role of PAF or LTB4. Finally, the presence of both neutrophils and eosinophils significantly increased superoxide anion generation in response to IL-8 as compared with that of eosinophils or neutrophils alone.
These results suggest that neutrophils can augment both trans-basement membrane migration and respiratory burst of eosinophils. This pathomechanism may contribute to the eventual manifestation of eosinophilic inflammation in the asthmatic airways.
Keywords: eosinophils, neutrophils, trans basement membrane migration, superoxide anion