Purification of Serum Proteins with Inhibitory Activity on the Histamine Release in vitro and/or in vivo

Abstract

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.

Cow’s milk protein β-lactoglobulin confers resilience against allergy by targeting complexed iron into immune cells

“…This is in line with the literature showing that depending on the degree of iron saturation, lactoferrin and transferrin can inhibit the degranulation capacity of cells in vitro and in vivo. [79][80][81]…”

Nutrition in chronic inflammatory conditions: Bypassing the mucosal block for micronutrients

“…306 Vice versa, import of ironsated transferrin, lactoferrin, and beta-lactoglobulin stabilizes mast cells and reduce their readiness for degranulation. 148,[307][308][309] To summarize, the most important aspect of iron deficiency is the general priming of immune cells, which react particularly sensitive to nutritional threats (Figure 4).…”

“…It is so effective, that there were even endeavors to use it instead of histamine as positive control for skin tests 306 . Vice versa, import of iron‐sated transferrin, lactoferrin, and beta‐lactoglobulin stabilizes mast cells and reduce their readiness for degranulation 148,307–309 …”

Desialylated transferrin in plasma of patients with migraine without aura

“…TF has been identified as one of the iron-binding proteins responsible for an inhibitory effect on histamine release from basophils and mast cells [19,20,33,34]. The dose-response curves in these studies revealed that inhibition of histamine release is dependent on the degree of TF iron saturation.…”