Mast Cell-Derived tumour Necrosis Factor is Essential for Allergic Airway Disease

¹ III. Medical Clinic, Dept of Pulmonary Medicine
² Division of Cell Biology, Dept of paediatrics, National Jewish Medical and Research Center, Denver, CO
³ Institute for Immunology, University of Mainz, Germany
⁴ III. Medical Clinic, Dept of Pulmonary Medicine; and Division of Cell Biology, Dept of paediatrics, National Jewish Medical and Research Center, Denver, CO

^* To whom correspondence should be addressed. E-mail: taube{at}3-med.klinik.uni-mainz.de.

	Abstract

Mast cells are thought to contribute to allergic airway disease. However, the role of mast cell produced mediators like TNF for the development of allergic airway disease is unclear.

To define the role of mast cells in acute allergic airway disease we studied 2 strains of mast cell deficient mice (Kit^W/Wv and Kit^W-sh/W-sh).

Compared to 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 sensitization 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 in sensitized and challenged wild-type mice. In contrast, sensitized 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.

These results demonstrate the significance of mast cells in the development of airway disease and highlight the importance of mast cell-derived TNF in these responses.