This broad based project has explored various expressions of allergy over the past 15 years, ranging from anaphylaxis to asthma and rhinitis. This past year, this project focused on aspects of non-immunologic mast cell activation by a histamine releasing factor derived from neutrophils (HRA- N). HRA-N activates mast cells to release histamine. but not to generate eicosanoids such as PGD2. The release of histamine was determined to be independent of eicosanoid production, as full histamine release can occur in response to IgE receptor mediated activation without any associated eicosanoid production. These data indicate that HRA-N and IgE activate mast cells through independent pathways. The response of mast cells to either IgE receptor mediated activation of HRA-N activation can be inhibited by exposure to corticosteriods, which are potent agents used to treat allergic diseases. A new agent for the treatment of asthma is an anti-allergic compound known as nedocromil. Nedocromil was found to reduce human neutrophil derived HRA-N production, providing an additional mechanism of action for this agent.
