Histamine-Releasing Factor and Immunoglobulins in Asthma and Allergy

Factors that can induce the release of histamine from basophils have been studied for more than 30 years. A protein termed histamine-releasing factor (HOE) was purified and molecularly cloned in 1995. HOE can stimulate histamine release and IL-4 and IL-13 production from IgE-sensitized basophils and mast cells. HOE-like activities were found in bodily fluids during the late phase of allergic reactions, implicating HOE in allergic diseases. However, definitive evidence for the role of HOE in allergic diseases has remained elusive. On the other hand, we found effects of monomeric IgE on the survival and activation of mast cells without the involvement of a specific antigen, as well as heterogeneity of IgEs in their ability to cause such effects. The latter property of IgE molecules seemed to be similar to the heterogeneity of IgEs in their ability to prime basophils in response to HOE. This similarity led to our recent finding that similar to 30% of IgE molecules can bind to HRF via their Fab interactions with two binding sites within the HOE molecule. The use of peptide inhibitors that block HRF-IgE interactions revealed an essential role of HOE to promote skin hypersensitivity and airway inflammation. This review summarizes this and more recent findings and provides a perspective on how they impact our understanding of allergy pathogenesis and potentially change the treatment of allergic diseases.