The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 2 June 2003. doi:10.1084/jem.20021806
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gonzalez-Espinosa, C.
Right arrow Articles by Rivera, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gonzalez-Espinosa, C.
Right arrow Articles by Rivera, J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© Rockefeller University Press, 0022-1007/2003/6/1453 $5.00
The Journal of Experimental Medicine, Volume 197, Number 11, 1453-1465

Preferential Signaling and Induction of Allergy-promoting Lymphokines Upon Weak Stimulation of the High Affinity IgE Receptor on Mast Cells

Claudia Gonzalez-Espinosa1,2, Sandra Odom1, Ana Olivera1, J. Peyton Hobson3, Maria Eugenia Cid Martinez2, Antonio Oliveira-dos-Santos4,5, Lillian Barra4,5, Sarah Spiegel3, Josef M. Penninger4,5 and Juan Rivera1

1 Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
2 Pharmacobiology Department, CINVESTAV Zona Sur, Calzada de los Tenorios 235, Mexico D.F., CP 14330 Mexico
3 Department of Biochemistry, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298
4 Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria
5 Ontario Cancer Institute, University Health Network and Departments of Medical Biophysics and Immunology, University of Toronto, M5G 2C1 Toronto, Canada

Address correspondence to Juan Rivera, NIAMS/NIH, Building 10, Room 9N228, Bethesda, MD 20892-1820. Phone: 301-496-7592; Fax: 301-480-1580; E-mail: juan_rivera{at}nih.gov

Mast cell degranulation and de novo cytokine production is a consequence of antigen-aggregation of the immunoglobulin E (IgE)-occupied high affinity receptor for IgE (Fc{varepsilon}RI). Herein, we report that lymphokines that promote allergic inflammation, like MCP-1, were potently induced at low antigen (Ag) concentrations or at low receptor occupancy with IgE whereas some that down-regulate this response, like interleukin (IL)-10, required high receptor occupancy. Weak stimulation of mast cells caused minimal degranulation whereas a half-maximal secretory response was observed for chemokines and, with the exception of TNF-{alpha}, a weaker cytokine secretory response was observed. The medium from weakly stimulated mast cells elicited a monocyte/macrophage chemotactic response similar to that observed at high receptor occupancy. Weak stimulation also favored the phosphorylation of Gab2 and p38MAPK, while LAT and ERK2 phosphorylation was induced by a stronger stimulus. Gab2-deficient mast cells were severely impaired in chemokine mRNA induction whereas LAT-deficient mast cells showed a more pronounced defect in cytokines. These findings demonstrate that perturbation of small numbers of IgE receptors on mast cells favors certain signals that contribute to a lymphokine response that can mediate allergic inflammation.

Key Words: cytokines • Gab2 • IgE • LAT • mast cells


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS