Purification of serum proteins with inhibitory activity on the histamine release in vitro and/or in vivo.

Recently, we described a factor in rat and human serum with inhibitory activity on the 2-hour passive cutaneous anaphylactic (PCA) reaction in rat skin. The Ca-ionophore-induced histamine release from rat peritoneal mast cells was inhibited as well. In human serum, inhibitory activity for the in vitro histamine release from rat mast cells was shown to be present within two serum fractions. One molecule was purified by 50-70% ammonium sulfate precipitation and subsequent DEAE chromatography at pH 5.4. The main component showed complete identity with transferrin. Commercially available transferrin was active in vitro as well. The dose-response plot revealed two inhibition maxima at transferrin concentrations of 0.05-5 ng/ml and at more than 1 mg/ml, respectively. Subsequently it was shown that the degree of iron saturation was critical for the decrease in histamine release. The mediator release in vivo (PCA) could not be inhibited by the iron transport protein. Inhibitory activity in vivo was however mediated by the second serum fraction, which was characterized by a molecular weight of approximately 150,000 daltons and an IEP within the alkaline range. These data suggest that exogenous factors may be potent modulators of inflammatory reactions.