Histamine-releasing factors and heterogeneity of IgE

Abstract

The duration and severity of the allergic response are variable. Even though antigens are rapidly cleared from the individual, an acute allergic response is frequently followed by a recrudescence of symptoms hours or even days after the initial exposure. Experimentally, the cellular infiltrates and mediators released during this late response resemble those associated with chronic inflammatory disease. Although basophils are present in this late reaction, the stimuli for their activation remain unknown. A heterogeneous group of unique cytokines called histamine-releasing factors (HRF), discovered over a decade ago, may well play a role in stimulating basophils during this late-phase reaction. These factors have been reported from a variety of cell sources including alveolar macrophages, platelets, vascular endothelial cells, B and T lymphocytes, mononuclear cell cultures, the U937 monocyte/macrophage-like cell line and the RPMI 8866 B cell line. These ubiquitous factors cause non-cytotoxic, calcium-dependent mediator release from human basophils in vitro and are also present and active in vivo. Purification attempts have revealed that HRF exists in at least three forms, based on molecular weight. In our hands, the mechanism of mediator release by one of the forms of HRF is IgE dependent. Since only about 50% of allergic donors' basophils respond to HRF, a heretofore unappreciated heterogeneity of IgE was revealed. The presence of HRF has been shown to correlate with severity of allergic disease in children with food allergies, with symptoms in the late-phase response in adults and with severity of the allergic response to an inhaled antigen. Thus, the study of HRF has evolved over the last decade and may lead to better understanding of the complex allergic response.