Assessment of the Functional Activities of Casein Phosphopeptides on Circulating Blood Leukocytes

One of the beneficial effects of peptide-rich protein hydrolysates on diverse pathological conditions has emerged from the concept that their intake as ingredients of dietary supplements or pharmaceutical preparations would have the potential to influence the inflammatory response. Leukocytes are physiologically and strategically positioned in the front line of the defense mechanisms and are the main protagonists of the inflammatory response. Their orchestral extravasation through sequential events that lead them to transmigrate across the endothelial barrier is the hallmark of inflammation. As the direct effects of the milk-derived bioactive molecules on circulating blood leukocyte behavior are still little understood and under explored, we have exposed freshly isolated human blood leukocytes to different caseinate-derived phosphopeptides (CPP) produced by trypsin digestion and studied their influence on cellular adhesiveness and mobilization, two of the most crucial leukocyte functions. We also observed their participation on a wound recovery model. The results herein presented and for the first time reported suggest that the CPP obtained by an enzymatic controlled hydrolysis are potential modulators of leukocyte adhesion by altering the expression of VLA-4 and VLA-5 integrins. CPP can also alter leukocyte trafficking by attracting or repelling them influencing, thus, the inflammatory response. In addition, these peptides might favor the recovery of wounds acting positively on fibroblast migration. Our results support the concept that CPP can add benefits for nutritional deficient patients through the enhancement of some crucial leukocyte functions mitigating the inflammatory components often present in malnutrition states.