Mast cells play a key role in the development of late airway hyperresponsiveness through TNF-α in a murine model of asthma

Young Suk Kim, Hyun Mi Ko, Nam In Kang, Chang Ho Song, Xin Zhang, Woo Chan Chung, Jae Hong Kim, In Hak Choi, Young Min Park, Gi Young Kim, Shun Young Im, Hern Ku Lee

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44 Citations (Scopus)

Abstract

We have investigated the role of TNF-α in mast cell-mediated late airway hyperresponsiveness (AHR) using mast cell-deficient WBB6F1-W/Wv (W/Wv) mice in a murine model of asthma, which exhibits a biphasic increase in AHR. TNF-α levels in the airway and magnitude of late AHR in response to airway allergen challenge were severely impaired in W/Wv mice compared to their littermates. In addition to TNF-α, cytosolic phospholipase A2 (cPLA2) phosphorylation and enzymatic activity in the lungs were also impaired in W/Wv mice. Either anti-TNF-α antibody or an inhibitor of cPLA2 abolished late AHR in congeneic +/+ mice. Intratracheal administration of TNF-α resulted in increases in late AHR, cPLA2 phosphorylation, cPLA2 activity, and phosphorylation of mitogen-activated protein kinases. Mast cell replacement restored airway TNF-α level, cPLA2 phosphorylation and enzymatic activity in the lungs as well as late AHR in W/Wv mice. These data indicate that mast cells play a key role in the development of late AHR through liberation of TNF-α.

Original languageEnglish
Pages (from-to)1107-1115
Number of pages9
JournalEuropean Journal of Immunology
Volume37
Issue number4
DOIs
Publication statusPublished - 2007 Apr

Keywords

  • Cytosolic phospholipase A
  • Late airway response
  • Mast cell
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Kim, Y. S., Ko, H. M., Kang, N. I., Song, C. H., Zhang, X., Chung, W. C., Kim, J. H., Choi, I. H., Park, Y. M., Kim, G. Y., Im, S. Y., & Lee, H. K. (2007). Mast cells play a key role in the development of late airway hyperresponsiveness through TNF-α in a murine model of asthma. European Journal of Immunology, 37(4), 1107-1115. https://doi.org/10.1002/eji.200636612