[Show abstract][Hide abstract] ABSTRACT: Anaphylaxis is an acute, severe, and potentially fatal systemic allergic reaction. Immunoglobulin E (IgE), mast cells, and histamine have long been associated with anaphylaxis, but an alternative pathway mediated by IgG has been suggested to be more important in the elicitation of anaphylaxis. Here, we showed that basophils, the least common blood cells, were dispensable for IgE-mediated anaphylaxis but played a critical role in IgG-mediated, passive and active systemic anaphylaxis in mice. In vivo depletion of basophils but not macrophages, neutrophils, or NK cells ameliorated IgG-mediated passive anaphylaxis and rescued mice from death in active anaphylaxis. Upon capture of IgG-allergen complexes, basophils released platelet-activating factor (PAF), leading to increased vascular permeability. These results highlight a pivotal role for basophils in vivo and contrast two major, distinct pathways leading to allergen-induced systemic anaphylaxis: one mediated by basophils, IgG, and PAF and the other "classical" pathway mediated by mast cells, IgE, and histamine.
[Show abstract][Hide abstract] ABSTRACT: Basophils circulate in the peripheral blood under physiological conditions, and they are recruited to affected tissues in allergic reactions, albeit in small numbers. Because of their rarity (less than 1% of peripheral blood leukocytes are basophils), and their similarity to mast cells, basophils have often been considered the lesser relatives of mast cells. Moreover, because basophils have been so difficult to identify, mice were erroneously believed for a long time to lack them. Therefore, the assumption that basophils have only redundant roles has remained unquestioned until recently. The flow-cytometric identification of basophils in mice and the development of in vivo models and reagents useful for their functional analyses have greatly advanced the field of basophil research. Previously unrecognized roles of basophils, dis-tinct from those of mast cells, have been shown in allergic responses and the regulation of acquired immunity. In this re-view, we mainly focus on roles of basophils in immediate-and delayed-onset allergic reactions. Basophils are crucial ini-tiators, rather than effectors, in the development of IgE-mediated, chronic cutaneous allergic inflammation, which is char-acterized by the massive infiltration of eosinophils and neutrophils and can be elicited even in the absence of mast cells and T cells. Basophils are dispensable for the induction of IgE-mediated systemic anaphylaxis, unlike mast cells, but play a major role in IgG-mediated passive and active systemic anaphylaxis, through the release of platelet-activating factor in response to stimulation with antigen-IgG immune complexes. Thus, basophils and their products appear to be promising therapeutic targets for allergic disorders.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.