concanavalin-a and tyrosyl-glycyl-glycine

The in vitro modulation of the proliferation of human peripheral blood lymphocytes by different synthetic peptides derived from milk proteins was investigated. Therefore, proliferation changes were followed up after incorporation of BrdU into the DNA, and the influence on protein biosynthesis was measured using the [3H]leucine incorporation test. Tyr-Gly and Tyr-Gly-Gly significantly enhanced (maximal 90 and 35%, respectively) the proliferation of PBL. For beta-casomorphin-7 and beta-casomorphin-10,lymphocyte proliferation was suppressed at lower concentrations, but stimulated at higher concentrations (> or = 10(-7) mol/l). Protein synthesis was stimulated (maxima at 25%) only with Tyr-Gly and Tyr-Gly-Gly. The findings point to a need for further studies on the possible function of peptides derived from milk proteins as orally bioavailable immunopotentiatory compounds.

Topics: Amino Acid Sequence; Bromodeoxyuridine; Caseins; Cell Division; Concanavalin A; Dipeptides; DNA; Endorphins; Humans; Leucine; Lymphocyte Activation; Lymphocytes; Milk Proteins; Molecular Sequence Data; Oligopeptides; Peptide Fragments

We have developed a system in which human peripheral blood mononuclear cells (PBMC) stimulated with concanavalin A (Con A) can be examined for regulatory cell activity upon coculture with responder cells undergoing mitogenic proliferation. Low concentrations of Con A resulted in the induction of helper function, while higher concentrations of Con A induced suppressor activity in the PBMC population. However, for each individual donor a particular concentration of Con A can be found at which point no regulatory cell activity is observed. This "balance point" provides a set of conditions under which the ability of an immunomodulator to up-regulate or down-regulate the system can be studied. The ability of leu-enkephalin to positively or negatively regulate an immune response was examined under these circumstances. The addition of leu-enkephalin to cultures stimulated by Con A at this balance point enhanced both suppressor cell (Ts) and helper cell (Th) activity in a concentration-dependent manner. The induction of Ts activity displayed a bimodal response at concentrations between 10(-12) to 10(-13) M and 10(-9) to 10(-10) M, while the induction of Th activity was consistently observed at 10(-11) M. Similar effects were seen with either of the peptides Tyr-Gly and Tyr-Gly-Gly, corresponding to the first two and three amino acids of the N-terminal ends of the enkephalins. Th activity was consistently enhanced at 10(-13) M Tyr-Gly-Gly and 10(-14) M Tyr-Gly. This suggests that leu-enkephalin may either positively or negatively regulate immune responses and that the intact leu-enkephalin molecule is not required for these effects.

Topics: Concanavalin A; Dose-Response Relationship, Drug; Drug Antagonism; Enkephalin, Leucine; Humans; Immunity; In Vitro Techniques; Oligopeptides; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory