Potentiation of human basophil histamine release by protamine: a new role for a polycation recognition site

Protamine is an arginine-rich basic polypeptide that stimulates histamine release from rat mast cells but not from human basophils. In this report, we show that protamine causes a non-cytolytic potentiation of IgE-mediated histamine release from human basophils. A direct effect of protamine on basophils was supported by results obtained using cell preparations containing 35-65% basophils. The potentiation occurred at all concentrations of antigen that initiated release and was most pronounced at antigen concentrations that alone stimulated minimal histamine release. The kinetics of potentiated release were parallel to those for IgE-mediated histamine release, and addition of protamine did not overcome the block caused by antigenic desensitization. Staging experiments indicated that enhancement occurred only when protamine and antigen were added together in a single step reaction. Protamine also potentiated release stimulated by eosinophil granule major basic protein or poly-L-lysine, but inhibited release initiated by poly-L-arginine; poly-L-arginine stimulated release was also inhibited by polymyxin B. Arginine-rich histone mimicked the protamine effect, while lysine-rich histone, polymyxin B, and compound 48/80 had minimal or no effect on IgE-mediated release. These results suggest that a polycation recognition site on human basophils similar to that described for rat mast cells may mediate potentiation of basophil secretory events by arginine-rich basic polypeptides.