Mast cells play a key role in Th2 cytokine-dependent asthma model through production of adhesion molecules by liberation of TNF-alpha.
10.3858/emm.2011.43.1.004
- Author:
Ok Hee CHAI
1
;
Eui Hyeog HAN
;
Hern Ku LEE
;
Chang Ho SONG
Author Information
1. Department of Anatomy, Chonbuk National University Medical School and Institute for Medical Sciences, Chonbuk National University, Jeonju 561-756, Korea. asch@jbnu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
asthma;
cell adhesion molecules;
mast cells;
models, animal;
ovalbumin;
Th2 cells;
tumor necrosis factor-alpha
- MeSH:
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
- From:Experimental & Molecular Medicine
2011;43(1):35-43
- CountryRepublic of Korea
- Language:English
-
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.
