ENDOGENOUS SUPERALLERGEN PROTEIN FV INDUCES IL-4 SECRETION FROM HUMANFC-EPSILON-RI+ CELLS THROUGH INTERACTION WITH THE V(H)3 REGION OF IGE

We investigated the mechanism whereby protein Fv (pFv), a human sialop rotein found in normal liver and largely released in the intestinal tr act in patients with viral hepatitis, induces mediator release from ba sophils and mast cells and evaluated whether it also induces IL-4 synt hesis and secretion in basophils, pFv is a potent stimulus for histami ne and IL-4 release from purified basophils. Histamine and IL-4 secret ion from basophils activated by pFv was significantly correlated (r(s) = 0.70; p < 0.001). There was also a correlation (r(s) = 0.58; p < 0. 01) between the maximum pFv- and anti-IgE-induced IL-4 release from ba sophils. The average t(1/2) for pFv-induced histamine release was lowe r (3.5 +/- 1.5 min) than for IL-4 release (79.5 +/- 8.5 min; p < 0.01) . IL-4 mRNA, constitutively present in basophils, was increased after stimulation by pFv and was inhibited by cyclosporin A and tacrolimus. Basophils from which IgE had been dissociated by brief exposure to lac tic acid no longer released IL-4 in response to pFv and anti-IgE. The response to an mAb cross-linking the alpha-chain of Fc epsilon RI was unaffected by this treatment. Three human V(H)3(+) monoclonal IgM conc entration-dependently inhibited pFv-induced secretion of IL-4 and hist amine from basophils and of histamine from human lung mast cells. In c ontrast, V(H)6(+) monoclonal IgM did not inhibit the release of IL-4 a nd histamine induced by pFv. These results indicate that pFv, which ac ts as an endogenous superallergen, interacts with the V(H)3 domain of IgE to induce the synthesis and release of IL-4 from human Fc epsilon RI+ cells.