L-amino acid oxidase plays a crucial role in host defense in the mammary glands.
The innate immune system plays an important role in protecting organs that are continuous with the outer surface of the body from bacterial infection. The antibacterial factors involved in this system have been sought in exocrine glands, particularly in the mammary glands. Because milk produced in the mammary glands is enriched in various nutrients, supporting the proliferation of bacteria, mammary glands appear to be at the greatest risk of bacterial infection and proliferation. Here, we show that mouse milk contains L-amino acid oxidase (LAO), a lactating mammary gland-specific protein that displays antibacterial activity in vitro through the production of hydrogen peroxide from free amino acids. We produced LAO-disrupted mouse lines to define the physiological properties and importance of the protein in vivo. The LAO-knockout mice were healthy and had normal mammary gland development; however, the antibacterial activity normally observed in milk from wild-type mice was absent from the milk of knockout mice. The content of free amino acids targeted by LAO was very low in wild-type milk, whereas these amino acids were abundant in LAO-knockout milk. Knockout mice exhibited weak resistance to an intramammary bacterial challenge compared to their wild-type counterparts. Further, preadministration of wild-type milk whey reduced the severity of bacterial infection in LAO-knockout mice. These results demonstrate that milk LAO protects the mammary gland against bacterial infection, and this antibacterial effect may be due to the generation of hydrogen peroxide by using free amino acids abundantly present in milk.
Nagaoka
Kentaro
K
Laboratory of Animal Breeding, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. akenaga@mail.ecc.u-tokyo.ac.jp
Aoki
Fugaku
F
Hayashi
Mizuna
M
Muroi
Yoshikage
Y
Sakurai
Toshihiro
T
Itoh
Kikuji
K
Ikawa
Masahito
M
Okabe
Masaru
M
Imakawa
Kazuhiko
K
Sakai
Senkiti
S
D000818:Animals; D001424:Bacterial Infections / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control; D005260:Female; D007113:Immunity, Innate; D050830:L-Amino Acid Oxidase / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D007774:Lactation / Q000276:immunology / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000201:enzymology* / Q000276:immunology* / Q000382:microbiology; D008413:Mastitis / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008892:Milk / Q000737:chemistry / Q000201:enzymology / Q000276:immunology; D013203:Staphylococcal Infections / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000276:immunology / Q000472:pathogenicity
D050830:L-Amino Acid Oxidase