Exp Mol Med.  2011 Jan;43(1):35-43. 10.3858/emm.2011.43.1.004.

Mast cells play a key role in Th2 cytokine-dependent asthma model through production of adhesion molecules by liberation of TNF-alpha

• Chai OH
• Han EH
• Lee HK
• Song CH

• KMID: 991621
• DOI: http://doi.org/10.3858/emm.2011.43.1.004

Abstract

Mast cells are well recognized as key cells in allergic reactions, such as asthma and allergic airway diseases. However, the effects of mast cells and TNF-alpha on T-helper type 2 (Th2) cytokine-dependent asthma are not clearly understood. Therefore, an aim of this study was to investigate the role of mast cells on Th2 cytokine-dependent airway hyperresponsiveness and inflammation. We used genetically mast cell-deficient WBB6F1/J-KitW/KitW-v (W/Wv), congenic normal WBB6F1/J-Kit+/Kit+ (+/+), and mast cell-reconstituted W/Wv mouse models of allergic asthma to investigate the role of mast cells in Th2 cytokine-dependent asthma induced by ovalbumin (OVA). And we investigated whether the intratracheal injection of TNF-alpha directly induce the expression of ICAM-1 and VCAM-1 in W/Wv mice. This study, with OVA-sensitized and OVA-challenged mice, revealed the following typical histopathologic features of allergic diseases: increased inflammatory cells of the airway, airway hyperresponsiveness, and increased levels of TNF-alpha, intercellular adhesion molecule (ICAM)-1, and vascular cellular adhesion molecule (VCAM)-1. However, the histopathologic features and levels of ICAM-1 and VCAM-1 proteins in W/Wv mice after OVA challenges were significantly inhibited. Moreover, mast cell-reconstituted W/Wv mice showed restoration of histopathologic features and recovery of ICAM-1 and VCAM-1 protein levels that were similar to those found in +/+ mice. Intratracheal administration of TNF-alpha resulted in increased ICAM-1 and VCAM-1 protein levels in W/Wv mice. These results suggest that mast cells play a key role in a Th2 cytokine-dependent asthma model through production of adhesion molecules, including ICAM-1 and VCAM-1, by liberation of TNF-alpha.

Keyword

asthma; cell adhesion molecules; mast cells; models, animal; ovalbumin; Th2 cells; tumor necrosis factor-alpha

MeSH Terms

Animals
Asthma/*immunology/metabolism/pathology
Blotting, Western
Bronchoalveolar Lavage Fluid/immunology
Cytokines/*immunology
Intercellular Adhesion Molecule-1/biosynthesis
Lung/immunology/pathology
Mast Cells/*immunology/metabolism
Mice
Ovalbumin
Th2 Cells/*immunology
Tumor Necrosis Factor-alpha/*metabolism
Vascular Cell Adhesion Molecule-1/biosynthesis