IMMUNOMODULATORY EFFECT OF BOVINE LACTOFERRIN PEPSIN HYDROLYSATE ON MURINE SPLENOCYTES AND PEYERS PATCH CELLS

The effects were examined of a pepsin hydrolysate of bovine lactoferri n on the proliferation of murine splenocytes. The hydrolysate enhanced [H-3]thymidine uptake by splenocytes, but undigested bovine lactoferr in exerted an inhibitory effect. The hydrolysate had the ability to in hibit the blastogenesis that was induced by mitogens such as concanava lin A, phytohemagglutinin, and lipopolysaccharide; inhibition was simi lar to that with undigested lactoferrin. These results suggested that the hydrolysate contained both immunostimulatory and immunoinhibitory peptides. The stimulatory effect of the hydrolysate in the absence of mitogens was then explored in more detail using nonadherent splenocyte s. The proliferative response of splenocytes to the hydrolysate was mu ch greater in the fraction that was enriched with B cells than in the fraction that was enriched with T cells. The hydrolysate did not affec t thymocyte proliferation. These data indicated that the adherent cell s resembling macrophages and found among the splenocytes were not the target cells of the hydrolysate. The stimulatory effect of the hydroly sate was due to the activation of B cells by the hydrolysate and enhan ced immunoglobulin production by splenocytes. Because the hydrolysate also enhanced the proliferation and immunoglobulin A production of Pey er's Patch cells, the immunostimulatory effect of the hydrolysate in v ivo was examined using mice that had been orally immunized with choler a toxin. The concentrations of immunoglobulin A conjugated against cho lera toxin in bile and in the intestinal contents of mice fed liquid d iets containing 1% (wt/vol) lactoferrin hydrolysate were greater than those of mice fed control diets. This result suggested that the use of the lactoferrin hydrolysate is beneficial to enhance mucosal immunity .