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Published ahead of print on August 11, 2004, doi:10.1164/rccm.200311-1610OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 9, November 2004, 952-959

A more recent version of this article appeared on November 1, 2004
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Submitted on November 25, 2003
Accepted on August 6, 2004

The Role of Virus-specific Immunoglobulin E in Airway Hyperresponsiveness

Azzeddine Dakhama1*, Jung-Won Park1, Christian Taube1, Kosuke Chayama1, Annette Balhorn1, Anthony Joetham1, Xu-Dong Wei1, Rhi-Hua Fan1, Christina Swasey1, Nobuaki Miyahara1, Taku Kodama1, Alberto Alvarez1, Katsuyuki Takeda1, and Erwin W Gelfand1

1 Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, USA

* To whom correspondence should be addressed. E-mail: dakhamaa{at}njc.org.

Respiratory syncytial virus is the most common cause of bronchiolitis during infancy and is associated with subsequent wheezing and asthma, but the nature of this association is not fully understood. We investigated the role of respiratory syncytial virus-specific immunoglobulin E antibodies in the pathophysiology of virus-induced airway dysfunction in a mouse model. Lung infection with respiratory syncytial virus resulted in significant increases in messenger ribonucleic acid expression for immunoglobulin E and both of its high affinity and low affinity receptors. In serum, virus-specific immunoglobulin E antibodies reached peak levels by day 21 following infection. Data from in vitro experiments show that respiratory syncytial virus can induce mast cell degranulation, but only if these cells are sensitized with specific immunoglobulin E. When passively sensitized in vivo with virus-specific immunoglobulin E, mice developed exaggerated airway responsiveness to methacholine upon airway infection, an effect that required the high affinity receptor of immunoglobulin E. These data suggest that respiratory syncytial virus-specific immunoglobulin E may contribute to the pathophysiolgy of airway dysfunction in children who develop this class of specific antibody.
Key words: Respiratory Syncytial Virus, Immunoglogulin E, Asthma, Airway function, Animal model




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