Endogenous superallergen protein Fv interacts with the V(H)3 region of IgEto induce cytokine secretion from human basophils

Background: Protein Fv is an endogenous protein, synthesized in liver and l argely released in the digestive tract during acute and chronic viral hepat itis, that binds to immunoglobulin (Ig) from various mammalian and nonmamma lian species, Methods: Basophils obtained from normal subjects were purified by a double Percoll gradient and elutriation, The secretion of histamine induced by pro tein Fv was assayed by a fluorometric technique, the extracellular protein levels of IL-4 and IL-13 were measured by ELISA, and IL-4 mRNA levels were evaluated by RT-PCR, Results: Protein Fv concentration-dependently induced histamine and IL-4 an d IL-13 release from purified basophils, IL-4 mRNA, constitutively present in basophils, was increased after stimulation by protein Fv, Histamine and IL-4 secretion from basophils, but not histamine and IL-13 release, activat ed by protein Fv was significantly correlated (r(s) = 0.70, p<0.001). Basop hils from which IgE had been dissociated by brief exposure to lactic acid n o longer released IL-4 in response to protein Fv and anti-IgE, Two preparat ions of human V(H)3(+) monoclonal IgM inhibited protein Fv-induced secretio n of IL-4 and histamine from basophils, In contrast, V(H)6(+) monoclonal Ig M did not inhibit the release of mediators caused by protein Fv, Conclusions: These results indicate that protein Fv, which acts as an endog enous superallergen, interacts with the V(H)3 domain of IgE to induce the s ynthesis and release of IL-4, IL-13 and the secretion of histamine from bas ophils.