Enzymatic digestion of the milk protein beta-casein releases potent chemotactic peptide(s) for monocytes and macrophages.
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.
Kitazawa
Haruki
H
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
Yonezawa
Kumiko
K
Tohno
Masanori
M
Shimosato
Takeshi
T
Kawai
Yasushi
Y
Saito
Tadao
T
Wang
Ji Ming
JM
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*
D002364:Caseins; D002630:Chemotactic Factors; D010455:Peptides; D010447:Peptide Hydrolases