This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 2007-0229OCv1 39/4/412    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cho, Y. S. Articles by Zhu, Z. Search for Related Content PubMed PubMed Citation Articles by Cho, Y. S. Articles by Zhu, Z.

Tyrosine Phosphatase SHP-1 in Oxidative Stress and Development of Allergic Airway Inflammation

¹ Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and ² Department of Allergy and Clinical Immunology, Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea

Correspondence and requests for reprints should be addressed to Zhou Zhu, M.D., Ph.D., Division of Allergy and Clinical Immunology, Johns Hopkins Asthma Allergy Center, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, 1A4, Baltimore, MD 21224. E-mail: zzhu{at}jhmi.edu

Oxidative stress has been implicated in allergic responses. SHP-1 is a target of oxidants and has been reported as a negative regulator in a mouse model of asthma. We investigated the effect of oxidative stress on the development of allergic airway inflammation in heterozygous viable motheaten (mev/+) mice deficient of SHP-1. Wild-type (WT) and mev/+ mice were compared in this study. Human alveolar epithelial cells (A549) transfected with mutant SHP-1 gene were used to evaluate the role of SHP-1 in lung epithelial cells. Hydrogen peroxide (H₂O₂) and Paraquat were used in vitro and in vivo, respectively. We also investigated whether mev/+ mice can break immune tolerance when exposed to aeroallergen intranasally. Compared with WT mice, bronchoalveolar lavage (BAL) cells and splenocytes from mev/+ mice showed a different response to oxidant stress. This includes a significant enhancement of intracellular reactive oxygen species and STAT6 phosphorylation in vitro and increased CCL20, decreased IL-10, and increased number of dendritic cells in BAL fluid in vivo. Mutant SHP-1-transfected epithelial cells secreted higher levels of CCL20 and RANTES after exposure to oxidative stress. Furthermore, break of immune tolerance, as development of allergic airway inflammation, was observed in mev/+ mice after allergen exposure, which was suppressed by antioxidant N-acetylcystein. These data suggest that SHP-1 plays an important role in regulating oxidative stress. Thus, increased intracellular oxidative stress and lack of SHP-1 in the presence of T helper cell type 2–prone cellular activation may lead to the development of allergic airway inflammation.

Key Words: SHP-1 • oxidative stress • allergen • asthma • immune tolerance

CLINICAL RELEVANCE Phosphatase SHP-1 plays an important role in regulating oxidative stress. Thus, increased intracellular oxidative stress and lack of SHP-1 in the presence of T helper cell type 2–prone cellular activation may lead to development of allergic airway inflammation.

 

This article has been cited by other articles:

				S. Y. Oh, T. Zheng, Y.-K. Kim, L. Cohn, R. J. Homer, A. N. J. McKenzie, and Z. Zhu A Critical Role of SHP-1 in Regulation of Type 2 Inflammation in the Lung Am. J. Respir. Cell Mol. Biol., May 1, 2009; 40(5): 568 - 574. [Abstract] [Full Text] [PDF]