Pretreatment with Low Levels of FcεRI-Crosslinking Stimulation Enhances Basophil Mediator Release.

Background: Basophils and mast cells are important initiator/effector cells capable of rapidly responding to IgE-mediated stimulation, but the precise mechanisms regulating their functions in vivo have not been fully identified. In this study, we assessed whether low levels of antigen can modulate activation of basophils and mast cells. Methods: Human basophils and cultured mast cells were pretreated with low concentrations of anti-FcεRI α-chain mAb (CRA-1 mAb), and their cell functions were assessed. Results: Basophils preincubated with CRA-1 mAb at as low as 1 ng/ml for 1 h showed significantly enhanced degranulation in response to various secretagogues such as MCP-1, FMLP, leukotriene B₄ and Ca ionophore A23187. FMLP-induced leukotriene C₄ production by basophils was also enhanced by CRA-1 mAb pretreatment. Degranulation was further enhanced when CRA-1 mAb-pretreated basophils were additionally treated with IL-3, IL-33 or leptin before stimulation with MCP-1. Priming by subthreshold CRA-1 mAb was a slow process, since 1 h of pretreatment was needed for maximal enhancement. Basophil priming also resulted from preincubation with subthreshold doses of an allergen, Der f 2. In parallel mAb experiments, CRA-1 mAb showed weak priming effects on human umbilical cord blood-derived cultured mast cells; a higher dose, 100 ng/ml, was necessary for this priming. Conclusion: These results indicate that subthreshold doses of CRA-1 mAb or allergens can prime basophils and induce exaggerated responses to various IgE-independent stimuli. This may be a potentially important mechanism that explains environmental allergen-induced exacerbation of IgE-mediated allergic diseases such as asthma. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]