Prostaglandin D2 as a mediator of allergic asthma.
Allergic asthma is caused by the aberrant expansion in the lung of T helper cells that produce type 2 (TH2) cytokines and is characterized by infiltration of eosinophils and bronchial hyperreactivity. This disease is often triggered by mast cells activated by immunoglobulin E (IgE)-mediated allergic challenge. Activated mast cells release various chemical mediators, including prostaglandin D2 (PGD2), whose role in allergic asthma has now been investigated by the generation of mice deficient in the PGD receptor (DP). Sensitization and aerosol challenge of the homozygous mutant (DP-/-) mice with ovalbumin (OVA) induced increases in the serum concentration of IgE similar to those in wild-type mice subjected to this model of asthma. However, the concentrations of TH2 cytokines and the extent of lymphocyte accumulation in the lung of OVA-challenged DP-/- mice were greatly reduced compared with those in wild-type animals. Moreover, DP-/- mice showed only marginal infiltration of eosinophils and failed to develop airway hyperreactivity. Thus, PGD2 functions as a mast cell-derived mediator to trigger asthmatic responses.
Matsuoka
T
T
Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan.
Hirata
M
M
Tanaka
H
H
Takahashi
Y
Y
Murata
T
T
Kabashima
K
K
Sugimoto
Y
Y
Kobayashi
T
T
Ushikubi
F
F
Aze
Y
Y
Eguchi
N
N
Urade
Y
Y
Yoshida
N
N
Kimura
K
K
Mizoguchi
A
A
Honda
Y
Y
Nagai
H
H
Narumiya
S
S
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003433:Crosses, Genetic; D005260:Female; D018390:Gene Targeting; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D015230:Prostaglandin D2 / Q000378:metabolism / Q000502:physiology*; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020545:Respiratory Mucosa / Q000378:metabolism
D000485:Allergens; D007378:Interleukins; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor