Prostaglandin D 2 as a Mediator of Allergic Asthma

Abstract

Allergic asthma is caused by the aberrant expansion in the lung of T helper cells that produce type 2 (T H 2) 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 D 2 (PGD 2 ), 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 T H 2 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, PGD 2 functions as a mast cell–derived mediator to trigger asthmatic responses.