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Mast cell-derived tumour necrosis factor is essential for allergic airway disease

¹ III. Medical Clinic, Dept of Pulmonary Medicine, and ³ Institute for Immunology, University of Mainz, Mainz, Germany. ² Division of Cell Biology, Dept of Paediatrics, National Jewish Medical and Research Center, Denver, CO, USA.

CORRESPONDENCE: C. Taube, III. Medical Clinic, Dept of Pulmonary Medicine, Johannes Gutenberg University, Langenbeckstr. 1, 55101 Mainz, Germany. Fax: 49 6131176668. E-mail: taube{at}3-med.klinik.uni-mainz.de

Keywords: Asthma, immunology, mast cell, tumour necrosis factor

Received: May 15, 2007
Accepted December 12, 2007

Mast cells are thought to contribute to allergic airway disease. However, the role of mast cell-produced mediators, such as tumour necrosis factor (TNF), for the development of allergic airway disease is unclear.

In order to define the role of mast cells in acute allergic airway disease two strains of mast cell-deficient mice (Kit_W/Wv and Kit_W-sh/W-sh) were studied.

Compared with their wild-type littermates, Kit_W/Wv and Kit_W-sh/W-sh mice developed significantly lower airway responsiveness to methacholine and less airway inflammation and goblet cell metaplasia, following sensitisation in the absence of adjuvant and airway challenge. Transfer of bone marrow-derived mast cells (BMMCs) from wild-type mice to Kit_W-sh/W-sh mice reconstituted both airway responsiveness and inflammation to levels similar to those in sensitised and challenged wild-type mice. In contrast, sensitised Kit_W-sh/W-sh mice reconstituted with BMMCs from TNF-deficient mice were still severely impaired in their ability to develop airway hyperresponsiveness, inflammation or goblet cell metaplasia following allergen challenge.

The present results demonstrate the significance of mast cells in the development of airway disease and highlight the importance of mast cell-derived tumour necrosis factor in these responses.

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