Background: Protein Fv is an endogenous protein, synthesized in liver and largely released in the digestive tract during acute and chronic viral hepatitis, that binds to immunoglobulin (Ig) from various mammalian and nonmammalian species. Methods: Basophils obtained from normal subjects were purified by a double Percoll gradient and elutriation. The secretion of histamine induced by protein 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 and 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, activated by protein Fv was significantly correlated (rs = 0.70, p<0.001). Basophils from which IgE had been dissociated by brief exposure to lactic acid no longer released IL–4 in response to protein Fv and anti–IgE. Two preparations of human VH3+ monoclonal IgM inhibited protein Fv–induced secretion of IL–4 and histamine from basophils. In contrast, VH6+ monoclonal IgM did not inhibit the release of mediators caused by protein Fv. Conclusions: These results indicate that protein Fv, which acts as an endogenous superallergen, interacts with the VH3 domain of IgE to induce the synthesis and release of IL–4, IL–13 and the secretion of histamine from basophils.

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