title: Enzymatic digestion of the milk protein beta-casein releases potent chemotactic peptide(s) for monocytes and macrophages.
abstract: Proteins in the milk release biologically active peptides upon enzymatic digestion. In the present study, we report the identification of novel monocyte/macrophage chemotactic peptides derived from enzymatically digested bovine beta-casein, a casein family member that is a major constituent of milk. Beta-casein fragments generated by actinase E showed potent chemotactic activity for human and mouse monocytes/macrophages, but not neutrophils, T lymphocytes or dendritic cells. The fragment-induced migration of human monocytes was inhibited by pertussis toxin and was not desensitized by a variety of known chemoattractants, suggesting that the digests activate a unique G protein-coupled receptor(s). The digests were further fractionated and purified to yield 3 small peptides. One peptide Q1 designated as "beta-casochemotide-1" with the amino acid sequence of YPVEP (f114-118 of beta-casein) induced high levels of macrophage chemotaxis. It also promoted calcium mobilization in macrophages, another indication of cell activation. Our study suggests that biologically active peptides released by actinase-digested milk beta-casein may promote innate host immune responses by inducing macrophage migration and activation.
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, USA. haruki@bios.tohoku.ac.jp
authors.forename: Haruki
authors.initials: H
authors.lastname: Kitazawa
authors.forename: Kumiko
authors.initials: K
authors.lastname: Yonezawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Tohno
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimosato
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawai
authors.forename: Tadao
authors.initials: T
authors.lastname: Saito
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
mesh_terms: D000818:Animals; D002364:Caseins / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D002630:Chemotactic Factors / Q000096:biosynthesis*; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000502:physiology*; D010455:Peptides / Q000378:metabolism*
chemical_list: D002364:Caseins; D002630:Chemotactic Factors; D010455:Peptides; D010447:Peptide Hydrolases