The role of virus-specific immunoglobulin E in airway hyperresponsiveness.
Respiratory syncytial virus (RSV) 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 RSV-specific IgE antibodies in the pathophysiology of virus-induced airway dysfunction in a mouse model. Lung infection with RSV resulted in significant increases in mRNA expression for IgE and both of its high- and low-affinity receptors. In serum, virus-specific IgE antibodies reached peak levels by Day 21 after infection. Data from in vitro experiments show that RSV can induce mast cell degranulation, but only if these cells are sensitized with specific IgE. When passively sensitized in vivo with virus-specific IgE, mice developed exaggerated airway responsiveness to methacholine on airway infection, an effect that required the high-affinity receptor of IgE. These data suggest that RSV-specific IgE may contribute to the pathophysiology of airway dysfunction in children who develop this class of specific antibody.
Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA. dakhamaa@njc.org
Azzeddine
A
Dakhama
Jung-Won
JW
Park
Christian
C
Taube
Kosuke
K
Chayama
Annette
A
Balhorn
Anthony
A
Joetham
Xu-Dong
XD
Wei
Rhi-Hua
RH
Fan
Christina
C
Swasey
Nobuaki
N
Miyahara
Taku
T
Kodama
Alberto
A
Alvarez
Katsuyuki
K
Takeda
Erwin W
EW
Gelfand
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis*; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D001483:Base Sequence; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000821:virology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000503:physiopathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D012680:Sensitivity and Specificity
D000914:Antibodies, Viral; D012333:RNA, Messenger; D007073:Immunoglobulin E